Selected publications

(1) The renin/ prorenin receptor (RER) - a novel signal transduction pathway

Nguyen G, Delarue F, Burcklé C, Bouzhir L, Giller T, Sraer JD (2002):
Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin.
J Clin Invest 109: 1417-1427 

Schefe JH, Menk M, Reinemund J, Effertz K, Hobbs RM, Pandolfi PP, Ruiz P, Unger T, Funke-Kaiser H (2006): 
A novel signal transduction cascade involving direct physical interaction of the renin/prorenin receptor with the transcription factor promyelocytic zinc finger protein.
Circ Res 99: 1355-1366 

Schefe JH, Neumann C, Goebel M, Danser J, Kirsch S, Gust R, Kintscher U, Unger T, Funke-Kaiser H (2008): 
Prorenin engages the (pro)renin receptor like renin and both ligand activities are unopposed by aliskiren.
J Hypertens 26: 1787-1794 

Kirsch S, Schrezenmeier E, Klare S, Zaade D, Seidel K, Schmitz J, Bernhard S, Slack M, Goldin-Lang P, Unger T, Zollmann F, Funke-Kaiser H (2014): 
The (pro)renin receptor ((P)RR) mediates constitutive, PLZF-independent pro-proliferative effects which are inhibited by bafilomycin but not genistein.
Int J Mol Med 33: 795-808 

Hermle T, Guida MC, Beck S, Helmstädter S, Simons M (2013):
Drosophila ATP6AP2/VhaPRR functions both as a novel planar cell polarity core protein and a regulator of endosomal trafficking.
EMBO J 32: 245-259

Kanda A, Noda K, Ishida S (2015):
ATP6AP2/(pro)renin receptor contributes to glucose metabolism via stabilizing the pyruvate dehydrogenase E1 beta subunit.
J Biol Chem 290: 9690-700 

(2) RER & cardiorenal end-organ damage

Ichihara A, Hayashi M, Kaneshiro Y, Suzuki F, Nakagawa T, Tada Y, Koura Y, Nishiyama A, Okada H, Uddin MN, Nabi AH, Ishida Y, Inagami T, Saruta T (2004):
Inhibition of diabetic nephropathy by a decoy peptide corresponding to the "handle" region for nonproteolytic activation of prorenin.
J Clin Invest 114: 1128-1135 

Ichihara A, Suzuki F, Nakagawa T, Kaneshiro Y, Takemitsu T, Sakoda M, Nabi AH, Nishiyama A, Sugaya T, Hayashi M, Inagami T (2006):
Prorenin receptor blockade inhibits development of glomerulosclerosis in diabetic angiotensin II type 1a receptor-deficient mice.
J Am Soc Nephrol 17: 1950-1961 

Burcklé CA, Jan Danser AH, Müller DN, Garrelds IM, Gasc JM, Popova E, Plehm R, Peters J, Bader M, Nguyen G (2006):
Elevated blood pressure and heart rate in human renin receptor transgenic rats.
Hypertension 47: 552-556 

Takahashi H, Ichihara A, Kaneshiro Y, Inomata K, Sakoda M, Takemitsu T, Nishiyama A, Itoh H (2007):
Regression of nephropathy developed in diabetes by (Pro)renin receptor blockade.
J Am Soc Nephrol 18: 2054-2061 

Kaneshiro Y, Ichihara A, Sakoda M, Takemitsu T, Nabi AH, Uddin MN, Nakagawa T, Nishiyama A, Suzuki F, Inagami T, Itoh H (2007):
Slowly progressive, angiotensin II-independent glomerulosclerosis in human (pro)renin receptor-transgenic rats.
J Am Soc Nephrol 18: 1789-1795 

Susic D, Zhou X, Frohlich ED, Lippton H, Knight M (2008):
Cardiovascular effects of prorenin blockade in genetically spontaneously hypertensive rats on normal and high-salt diet.
Am J Physiol Heart Circ Physiol 295: H1117-H1121 

Siragy HM, Huang J (2008):
Renal (pro)renin receptor upregulation in diabetic rats through enhanced angiotensin AT1 receptor and NADPH oxidase activity.
Exp Physiol 93: 709-714 

Melnyk RA, Tam J, Boie Y, Kennedy BP, Percival MD (2009):
Renin and prorenin activate pathways implicated in organ damage in human mesangial cells independent of angiotensin II production.
Am J Nephrol 30: 232-243 

Hirose T, Hashimoto M, Totsune K, Metoki H, Asayama K, Kikuya M, Sugimoto K, Katsuya T, Ohkubo T, Hashimoto J, Rakugi H, Takahashi K, Imai Y (2009):
Association of (pro)renin receptor gene polymorphism with blood pressure in Japanese men: the Ohasama study.
Am J Hypertens 22: 294-299 

Muhlestein JB, May HT, Bair TL, Prescott MF, Horne BD, White R, Anderson JL (2010):
Relation of elevated plasma renin activity at baseline to cardiac events in patients with angiographically proven coronary artery disease.
Am J Cardiol 106: 764-769 

Sihn G, Rousselle A, Vilianovitch L, Burckle C, Bader M (2010):
Physiology of the (pro)renin receptor: Wnt of change?
Kidney Int 78: 246-256    

Funke-Kaiser H, Zollmann FS, Schefe JH, Unger T (2010): 
Signal transduction of the (pro)renin receptor as a novel therapeutic target for preventing end-organ damage.
Hypertens Res 33: 98-104   

Seki Y, Ichihara A, Mizuguchi Y, Sakoda M, Kurauchi-Mito A, Narita T, Kinouchi K, Bokuda K, Itoh H (2010):
Add-on blockade of (pro)renin receptor in imidapril-treated diabetic SHRsp.
Front Biosci (Elite Ed) 2: 972-979 

Balakumar P, Jagadeesh G (2011):
Potential cross-talk between (pro)renin receptors and Wnt/frizzled receptors in cardiovascular and renal disorders.
Hypertens Res 34:1161-1170   

Mahmud H, Silljé HH, Cannon MV, van Gilst WH, de Boer RA (2012):
Regulation of the (pro)renin-renin receptor in cardiac remodelling.
J Cell Mol Med 16: 722-729 

Batenburg WW, Danser AH (2012):
(Pro)renin and its receptors: pathophysiological implications.
Clin Sci (Lond) 123: 121-133   

Moilanen AM, Rysä J, Serpi R, Mustonen E, Szabò Z, Aro J, Näpänkangas J, Tenhunen O, Sutinen M, Salo T, Ruskoaho H (2012):
(Pro)renin receptor triggers distinct angiotensin II-independent extracellular matrix remodeling and deterioration of cardiac function.
PLoS One 7: e41404 

Wang N, Frank GD, Ding R, Tan Z, Rachakonda A, Pandolfi PP, Senbonmatsu T, Landon EJ, Inagami T (2012):
Promyelocytic leukemia zinc finger protein activates GATA4 transcription and mediates cardiac hypertrophic signaling from angiotensin II receptor 2.
PLoS One 7: e35632 

Fukushima A, Kinugawa S, Takada S, Matsushima S, Sobirin MA, Ono T, Takahashi M, Suga T, Homma T, Masaki Y, Furihata T, Kadoguchi T, Yokota T, Okita K, Tsutsui H (2014):
(Pro)renin receptor in the skeletal muscle is involved in the development of insulin resistance associated with post-infarct heart failure in mice.
Am J Physiol Endocrinol Metab 307: E503-514 

Liu FY, Liu XY, Zhang LJ, Cheng YP, Jiang YN (2014):
Binding of prorenin to (pro)renin receptor induces the proliferation of human umbilical artery smooth muscle cells via ROS generation and ERK1/2 activation.
J Renin Angiotensin Aldosterone Syst 15: 99-108 

Saito S, Shimizu H, Yisireyili M, Nishijima F, Enomoto A, Niwa T (2014):
Indoxyl sulfate-induced activation of (pro)renin receptor is involved in expression of transforming growth factor-beta1 and alpha-smooth muscle actin in proximal tubular cells.
Endocrinology 155: 1899-1907 

Yisireyili M, Saito S, Abudureyimu S, Adelibieke Y, Ng HY, Nishijima F, Takeshita K, Murohara T, Niwa T. (2014):
Indoxyl sulfate-induced activation of (pro)renin receptor promotes cell proliferation and tissue factor expression in vascular smooth muscle cells.
PLoS One 9: e109268 

Lee DY, Kim HS, Won KJ, Lee KP, Jung SH, Park ES, Choi WS, Lee HM, Kim B (2014): 
DJ-1 regulates the expression of renal (pro)renin receptor via reactive oxygen species-mediated epigenetic modification.
Biochim Biophys Acta 1850: 426-434 

Lian H, Wang X, Wang J, Liu N, Zhang L, Lu Y, Yang Y, Zhang L (2015):
Heart-specific overexpression of (pro)renin receptor induces atrial fibrillation in mice.
Int J Cardiol 184C: 28-35 

Haque R, Hur EH, Farrell AN, Iuvone PM, Howell JC (2015):
MicroRNA-152 represses VEGF and TGFbeta1 expressions through post-transcriptional inhibition of (pro)renin receptor in human retinal endothelial cells.
Mol Vis 21: 224-235 

Li C, Siragy HM (2015):
(Pro)renin receptor regulates autophagy and apoptosis in podocytes exposed to high glucose.
Am J Physiol Endocrinol Metab 309: E302-310 

Ramkumar N, Stuart D, Calquin M, Quadri S, Wang S, Van Hoek AN, Siragy HM, Ichihara A, Kohan DE (2015):
Nephron-specific deletion of the prorenin receptor causes a urine concentration defect. 
J Physiol Renal Physiol 309: F48-56 

Wang F, Lu X, Liu M, Feng Y, Zhou SF, Yang T (2015):
Renal medullary (pro)renin receptor contributes to angiotensin II-induced hypertension in rats via activation of the local renin-angiotensin system.
BMC Med 13: 278 

Ellmers LJ, Rademaker MT, Charles CJ, Yandle TG, Richards AM (2016):
(Pro)renin receptor blockade ameliorates cardiac injury and remodeling and improves function after myocardial infarction.
J Card Fail 22: 64-72 

Liu Y, Zuo S, Li X, Fan J, Cao X, Yu X, Yang Q (2016):
Interaction between V-ATPase B2 and (pro) renin receptors in promoting the progression of renal tubulointerstitial fibrosis.
Sci Rep 6: 25035. 

Shamansurova Z, Tan P, Ahmed B, Pepin E, Seda O, Lavoie JL (2016):
Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight.
Mol Metab 5: 959-969   

Narumi K, Sato E, Hirose T, Yamamoto T, Nakamichi T, Miyazaki M, Sato H, Ito S (2018):
(Pro)renin receptor is involved in mesangial fibrosis and matrix expansion.
Sci Rep 8: 16. 

Nishijima T, Ohba K, Baba S, Kizawa T, Hosokawa K, Endo F, Yamashiro Y, Suwabe A, Sasaki A, Takahashi K, Sakurai S (2018):
Decrease of plasma soluble (pro)renin receptor by bariatric surgery in patients with obstructive sleep apnea and morbid obesity.
Metab Syndr Relat Disord Mar 20 [epub] 

Gong L, Zhang S, Li L, Gao X, Wang D, Wu D, Wang K, Liu Y (2018):
Elevated plasma soluble (pro)renin receptor levels are associated with left ventricular remodeling and renal function in chronic heart faiure patients with reduced ejection fraction.
Peptides Apr 13 [epub] 

Fang H, Deng M, Zhang L, Lu A, Su J, Xu C, Zhou L, Wang L, Ou JS, Wang W, Yang T (2018):
Role of (pro)renin receptor in albumin overload-induced nephropathy in rats.
Am J Physiol Renal Physiol May 30 [epub] 

Quadri SS, Culver S, Ramkumar N, Kohan DE, Siragy HM (2018):
(Pro)renin receptor mediates obesity-induced antinatriuresis and elevated blood pressure via upregulation of the renal epithelial sodium channel.
PLoS One 13: e0202419 

Wu J, Zhang C, Liu C, Zhang A, Li A, Zhang J, Zhang Y:
Aortic constriction induces hypertension and cardiac hypertrophy via (pro)renin receptor activation and the PLC-β3 signaling pathway.
Mol Med Rep 2018 Nov 13 [epub]

Yoshida A, Kanamori H, Naruse G, Minatoguchi S, Iwasa M, Yamada Y, Mikami A, Kawasaki M, Nishigaki K, Minatoguchi S:
(Pro)renin receptor blockade ameliorates heart failure caused by chronic kidney disease.
J Card Fail 2019 Feb 12 [epub]

Dong X, Yu S, Wang Y, Yang M, Xiong J, Hei N, Dong B, Su Q, Chen J:
(Pro)renin receptor-mediated myocardial injury, apoptosis, and inflammatory response in rats with diabetic cardiomyopathy.
J Biol Chem 2019 Apr 5 [epub]

Cao X, Yu S, Wang Y, Yang M, Xiong J, Yuan H, Dong B (2019):
Effects of the (pro)renin receptor on cardiac remodeling and function in a rat alcoholic cardiomyopathy model via the PRR-ERK1/2-NOX4 pathway.
Oxid Med Cell Longev 546975.

Li C, Matavelli LC, Akhtar S, Siragy HM (2019):
(Pro)renin receptor contributes to renal mitochondria dysfunction, apoptosis and fibrosis in diabetic mice.
Sci Rep 9: 11667.

Xiong J, Cao X, Qiao S, Yu S, Li L, Yu Y, Fu C, Jiang F, Dong B, Su Q:
(Pro)renin receptor is involved in myocardial damage in alcoholic cardiomyopathy.
Alcohol Clin Exp Res 2019 Sep 9 [epub]

Akhtar S, Siragy HM (2019):
Pro-renin receptor suppresses mitochondrial biogenesis and function via AMPK/SIRT-1/PGC-1α pathway in diabetic kidney.
PLoS One 14: e0225728.

Ma H, Dong X, Cao X, Hei N, Li J, Wang Y, Kong J, Dong B:
Pro-renin receptor (PRR) overexpression promotes angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E knockout mice.
Hum Gene Ther 2020 Jan 28 [epub]

Cho HM, Kim I:
Maternal high-fructose intake induces hypertension through activating histone codes on the (pro)renin receptor promoter.
Biochem Biophys Res Commun 2020 May 15 [epub]

Wang F, Sun Y, Luo R, Lu X, Yang B, Yang T:
COX-2-independent activation of renal (pro)renin receptor contributes to DOCA-salt hypertension in rats.
Am J Physiol Renal Physiol 2020 Aug 17 [epub]

Luo R, Yang KT, Wang F, Xu C, Yang T:
A (pro)renin receptor decoy peptide PRO20 protects against adriamycin-induced nephropathy by targeting intrarenal renin-angiotensin system.
Am J Physiol Renal Physiol 2020 Aug 31 [epub]

Yu S, Dong X, Yang M, Yu Q, Xiong J, Chen J, Dong B, Su Q (2021):
(Pro)renin receptor involves in myocardial fibrosis and oxidative stress in diabetic cardiomyopathy via the PRR-YAP pathway.
Sci Rep 11: 3259.

Fu Z, Wang F, Liu X, Hu J, Su J, Lu X, Lu A, Cho JM, Symons JD, Zou CJ, Yang T:
Soluble (pro)renin receptor induces endothelial dysfunction and hypertension in mice with diet-Induced obesity via activation of angiotensinII type 1 receptor.
Clin Sci (Lond) 2021 Feb 24 [epub]

Ramkumar N, Stuart D, Peterson CS, Hu C, Wheatley W, Cho JM, Symons JD, Kohan DE:
Loss of soluble (pro)renin receptor attenuates angiotensin-II induced hypertension and renal injury.
Circ Res 2021 Apr 23 [epub]

Wang F, Chen Y, Zou CJ, Luo R, Yang T:
Mutagenesis of the cleavage site of pro renin receptor abrogates angiotensin II-induced hypertension in mice.
Hypertension 2021 May 24 [epub]

Wang Y, Wang Y, Xue K, Wang H, Zhou J, Gao F, Li C, Yang T, Fang H. (2021):
(Pro)renin receptor antagonist PRO20 attenuates nephrectomy-induced nephropathy in rats via inhibition of intrarenal RAS and Wnt/β-catenin signaling.
Physiol Rep 9: e14881.

Gogulamudi VR, Arita DY, Bourgeois CRT, Jorgensen J, He J, Wimley WC, Satou R, Gonzalez AA, Prieto MC (2021):
High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct.
Sci Rep 11: 13815.

Amari Y, Morimoto S, Suda C, Iida T, Okuda H, Yurugi T, Oyama Y, Aoyama N, Nakajima F, Ichihara A (2021):
Serum soluble (pro)renin receptor level as a prognostic factor in patients undergoing maintenance hemodialysis.
Sci Rep 11: 17402.

Saigo S, Kino T, Uchida K, Sugawara T, Chen L, Sugiyama M, Azushima K, Wakui H, Tamura K, Ishigami T (2021):
Blood pressure elevation of tubular specific (P)RR transgenic mice and lethal tubular degeneration due to possible intracellular interactions between (P)RR and alternative renin products.
Int J Mol Sci 23: 302.

Gladysheva IP, Sullivan RD, Ramanathan K, Reed GL (2022):
Soluble (pro)renin receptor levels are regulated by plasma renin activity and correlated with edema in mice and humans with HFrEF.
Biomedicines 10: 1874.

Zhang J, Cheng YJ, Luo CJ, Yu J (2022):
Inhibitory effect of (pro)renin receptor decoy inhibitor PRO20 on endoplasmic reticulum stress during cardiac remodeling.
Front Pharmacol 13: 940365.

Hsieh YC, Wu PS, Lin YT, Huang YH, Hou MC, Lee KC, Lin HC (2022):
(Pro)renin receptor inhibition attenuated liver steatosis, inflammation, and fibrosis in mice with steatohepatitis.
FASEB J 36: e22526.

Fu Z, Zheng H, Kaewsaro K, Lambert J, Chen Y, Yang T:
Mutagenesis of the cleavage site of (pro)renin receptor abrogates aldosterone-salt-induced hypertension and renal injury in mice.
Am J Physiol Renal Physiol 2022 Oct 27 [epub]

Gayban AJB, Souza LAC, Cooper SG, Regalado E, Kleemann R, Feng Earley Y (2023):
(Pro)renin receptor antagonism attenuates high-fat-diet-induced hepatic steatosis.
Biomolecules 13: 142.

Fang H, Yang T, Zhou B, Li X (2023):
(Pro)renin receptor decoy peptide PRO20 protects against oxidative renal damage induced by advanced oxidation protein oroducts.
Molecules 28: 3017.

Xie S, Song S, Liu S, Li Q, Zou W, Ke J, Wang C (2024):
(Pro)renin receptor mediates tubular epithelial cell pyroptosis in diabetic kidney disease via DPP4-JNK pathway.
J Transl Med 22: 26.

Pan S, A C Souza L, Worker CJ, Reyes Mendez ME, Gayban AJB, Cooper SG, Sanchez Solano A, Bergman RN, Stefanovski D, Morton GJ, Schwartz MW, Feng Earley Y (2024):
(Pro)renin receptor signaling in hypothalamic tyrosine hydroxylase neurons is required for obesity-associated glucose metabolic impairment.
JCI Insight e174294.

Zhang X, Dong X, Jie H, Li S, Li H, Su Y, Li L, Kang L, Dong B, Zhang Y (2024):
Downregulation of the (pro)renin receptor alleviates ferroptosis-associated cardiac pathological changes via the NCOA 4-mediated ferritinophagy pathway in diabetic cardiomyopathy.
Int Immunopharmacol 138: 112605.

Luo R, Yang KT, Wang F, Zheng H, Yang T:
Collecting duct pro(renin) receptor contributes to unilateral ureteral obstruction-induced kidney injury via activation of the intrarenal RAS.
Hypertension 2024 Aug 22 [epub]

Zhang N, Song X, Bian Y, Bai R, Yang H, Wang G, Li H, Xiao C (2024):
Renin and (pro)renin receptors induce vascular smooth muscle cell proliferation and neointimal hyperplasia by activating oxidative stress and inflammation.
Vasc Med 1358863X241261368.

Zhu M, Yi X, Song S, Yang H, Yu J, Xu C (2024):
Principle role of the (pro)renin receptor system in cardiovascular and metabolic diseases: An update.
Cell Signal 111417.  

Lin M, Wang D, Chen Y. Chen G, Zhou Y, Ou J, Xiao L (2024):
PRR promotes hypertensive renal injury by activating Wnt/beta-catenin signaling and inflammation infiltration in mice.
Biochim Biophys Acta Mol Basis Dis 167517.

Larenas PE, Cardenas P, Aguirre-Delgadillo M, Moris C, Casarini DE, Vallotton Z, Prieto MC, Gonzalez AA (2024):
GLUT1 and prorenin receptor mediate differential regulation of TGF-β and CTGF in renal inner medullary collecting duct cells during high glucose conditions.
Biol Res 57: 81.

Li S, Zhang J, Zhao Y, Kang L, Jie H, Dong B (2024):
(Pro)renin receptor aggravates myocardial pyroptosis in diabetic cardiomyopathy through AMPK-NLRP3 pathway.
Front Pharmacol 15: 1453647.

(3) RER & oncology

Uraoka M, Ikeda K, Nakagawa Y, Koide M, Akakabe Y, Nakano-Kurimoto R, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H (2009):
Prorenin induces ERK activation in endothelial cells to enhance neovascularization independently of the renin-angiotensin system.
Biochem Biophys Res Commun 390: 1202-1207 

Cruciat CM, Ohkawara B, Acebron SP, Karaulanov E, Reinhard C, Ingelfinger D, Boutros M, Niehrs C (2010):
Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling.
Science 327: 459-463 

Bernhard SM, Seidel K, Schmitz J, Klare S, Kirsch S, Schrezenmeier E, Zaade D, Meyborg H, Goldin-Lang P, Stawowy P, Zollmann FS, Unger T, Funke-Kaiser H (2012): 
The (pro)renin receptor ((P)RR) can act as a repressor of Wnt signalling.
Biochem Pharmacol 84: 1643-1650 

Yamamoto H, Kaneko K, Ohba K, Morimoto R, Hirose T, Satoh F, Totsune K, Takahashi K (2013):
Increased expression of (pro)renin receptor in aldosterone-producing adenomas.
Peptides 49: 68-73

Ohba K, Suzuki T, Nishiyama H, Kaneko K, Hirose T, Totsune K, Sasano H, Takahashi K (2014)
Expression of (pro)renin receptor in breast cancers and its effect on cancer cell proliferation.
Biomed Res 35: 117-126

Kong XM, Zhang GH, Huo YK, Zhao XH, Cao DW, Guo SF, Li AM, Zhang XR (2015):
MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2.
Int J Clin Exp Pathol 8: 12845-12852 

Shibayama Y, Fujimori T, Nguyen G, Hirose T, Totsune K, Ichihara A, Kitada K, Nakano D, Kobori H, Kohno M, Masaki T, Suzuki Y, Yachida S, Nishiyama A (2015):
(Pro)renin receptor is crucial for Wnt/beta-catenin-dependent genesis of pancreatic ductal adenocarcinoma.
Sci Rep 5: 8854

Tani Y, Yamada S, Inoshita N, Hirata Y, Shichiri M (2015):
Regulation of growth hormone secretion by (pro)renin receptor.
Sci Rep 5: 10878

Wang J, Shibayama Y, Nakano D, Hitomi H, Nishiyama A (2016):
Role of (pro) renin Receptor in the activation of Wnt/ Β-Catenin pathway in colon cancer.
J Hypertens 34 Suppl 1 - ISH 2016 Abstract Book: e216

Featherston T, Yu HH, Dunne JC, Chibnall AM, Brasch HD, Davis PF, Tan ST, Itinteang T. (2016):
Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System.
Front Surg 3: 52

Bradshaw AR, Wickremesekera AC, Brasch HD, Chibnall AM, Davis PF, Tan ST, Itinteang T (2016):
Glioblastoma Multiforme Cancer Stem Cells Express Components of the Renin-Angiotensin System.
Front Surg 3: 51

Nishiyama A, Suzuki F (22.7.2015):
Cancer marker and application thereof.
PATENT APPLICATION EP 2 896 692 A1 

Delforce SJ, Lumbers ER, Corbisier de Meautsart C, Wang Y, Proietto A, Otton G, Scurry J, Verrills NM, Scott RJ, Pringle KG (2016):
Expression of renin angiotensin system (RAS) components in endometrial cancer.
Endocr Connect 2016 Dec 12 

Arundhathi A, Chuang WH, Chen JK, Wang SE, Shyr YM, Chen JY, Liao WN, Chen HW, Teng YM, Pai CC, Wang CH (2016):
Prorenin receptor acts as a potential molecular target for pancreatic ductal adenocarcinoma diagnosis.
Oncotarget 7: 55437-55448 

Wang J, Shibayama Y, Zhang A, Ohsaki H, Asano E, Suzuki Y, Kushida Y, Kobara H, Masaki T, Wang Z, Nishiyama A:
(Pro)renin receptor promotes colorectal cancer through the Wnt/beta-catenin signalling pathway despite constitutive pathway component mutations.
Br J Cancer 2018 Dec 17  [epub]

van Schaijik B, Tan ST, Marsh RW, Itinteang T:
Expression of the (pro)renin receptor and its effect on endothelial cell proliferation in infantile hemangioma.
Pediatr Res 2019 May 15 [epub]

Humphries H, Brasch HD, van Schaijik B, Tan ST, Itinteang T:
Expression of components of the renin-angiotensin system by embryonic stem cell-like population within keloid lesions.
Plast Reconstr Surg 2019 May 7 [epub]

Beitia M, Solano-Iturri JD, Errarte P, Calvete-Candenas J, Loizate A, Etxezarraga MC, Sanz B, Larrinaga G (2019):
(Pro)renin receptor expression increases throughout the colorectal adenoma-adenocarcinoma sequence and it is associated with worse colorectal cancer prognosis.
Cancers (Basel) 11: 881.

Mohammad AH, Assadian S, Couture F, Lefebvre KJ, El-Assaad W, Barrès V, Ouellet V4, Boulay PL, Yang J, Latour M, Furic L, Muller W, Sonenberg N, Mes-Masson AM, Saad F, Day R, Teodoro J (2019):
V-ATPase-associated prorenin receptor is upregulated in prostate cancer after PTEN loss.
Oncotarget 10: 4923-4936

Wang J, Nishiyama A, Matsuyama M, Wang Z, Yuan Y (2020):
The (pro)renin receptor: a novel biomarker and potential therapeutic target for various cancers.
Cell Commun Signal 18: 39.  

Endo M, Ohba K, Sato S, Yokota Y, Takahashi K:
Increased soluble (pro)renin receptor protein by autophagy inhibition in cultured cancer cells.
Genes Cells 2020 Apr 20 [epub]

Mohammad AH, Kim SH, Bertos N, El-Assaad W, Nandi I, Smith H, Yang J, Chen O, Gamache I, Rao T, Gagnon B, Gruosso T, Tremblay ML, Sonenberg N, Guiot MC, Muller W, Park M, Teodoro JG:
Elevated V-ATPase activity following PTEN loss is required for enhanced oncogenic signaling in breast cancer.
Mol Cancer Res 2020 Jun 25 [epub]

Ohba K, Endo M, Sato S, Kashio-Yokota Y, Hirose T, Takahashi K:
(Pro)renin receptor/ATP6AP2 is required for autophagy and regulates proliferation in lung adenocarcinoma cells.
Genes Cells 2020 Oct 5 [epub]

Zhao K, Wang M, Wu A (2020):
ATP6AP2 is overexpressed in breast cancer and promotes breast cancer progression.
Cancer Manag Res 12: 10449-10459

Shibayama Y, Takahashi K, Yamaguchi H, Yasuda J, Yamazaki D, Rahman A, Fujimori T, Fujisawa Y, Takai S, Furukawa T, Nakagawa T, Ohsaki H, Kobara H, Wong JH, Masaki T, Yuzawa Y, Kiyomoto H, Yachida S, Fujimoto A, Nishiyama A (2020):
Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H.
Commun Biol 3: 724.

Siljee S, Buchanan O, Brasch HD, Bockett N, Patel J, Paterson E, Purdie GL, Davis PF, Itinteang T, Tan ST (2021):
Cancer stem cells in metastatic head and neck cutaneous squamous cell carcinoma express components of the renin-angiotensin system.
Cells 10: 243.

Solano-Iturri JD, Echevarría E, Unda M, Loizaga-Iriarte A, Perez-Fernandez A, Angulo JC, Lopez JI, Larrinaga G (2021):
Clinical implications of (pro)renin receptor (PRR) expression in renal tumours.
Diagnostics (Basel) 11: 272.

Swensen AC, He J, Fang AC, Ye Y, Nicora CD, Shi T, Liu AY, Sigdel TK, Sarwal MM, Qian WJ (2021):
A comprehensive urine proteome database generated from patients with various renal conditions and prostate cancer.
Front Med (Lausanne) 8: 548212.

Siljee S, Milne B, Brasch HD, Bockett N, Patel J, Davis PF, Kennedy-Smith A, Itinteang T, Tan ST (2021):
Expression of components of the renin-angiotensin system by cancer stem cells in renal clear cell carcinoma.
Biomolecules 11: 537.

Munro MJ, Peng L, Wickremesekera SK, Tan ST (2021):
Colon adenocarcinoma-derived cells possessing stem cell function can be modulated using renin-angiotensin system inhibitors.
PLoS One 16: e0256280.

Morosin SK, Delforce SJ, Kahl RGS, Corbisier de Meaultsart C, Lumbers ER, Pringle KG:
The (pro)renin receptor and soluble (pro)renin receptor in choriocarcinoma.
Reproduction. 2021 Aug 1 [epub]

Kashio-Yokota Y, Sato S, Hirose T, Watanabe T, Endo A, Watanabe F, Endo M, Ohba K, Mori T, Takahashi K (2021):
Elevated (pro)renin receptor expression by anti-cancer drugs, carboplatin and paclitaxel, in cultured cancer cells: Possible involvement of apoptosis and autophagy.
Tohoku J Exp Med 255: 91-104

Larrinaga G, Calvete-Candenas J, Solano-Iturri JD, Martin AM, Pueyo A, Nunes-Xavier CE, Pulido R, Dorado JF, Lopez JI, Angulo JC (2021):
(Pro)renin receptor is a novel independent prognostic marker in invasive urothelial carcinoma of the bladder.
Cancers (Basel) 13: 5642.

Qi C, Lei L, Hu J, Wang G, Liu J, Ou S:
Identification of a five-gene signature deriving from the vacuolar ATPase (V-ATPase) sub-classifies gliomas and decides prognoses and immune microenvironment alterations.
Cell Cycle 2022 Mar 10 [epub]

Martin JH, Mohammed R, Delforce SJ, Skerrett-Byrne DA, de Meaultsart CC, Almazi JG, Stephens AN, Verrills NM, Dimitriadis E, Wang Y, Lumbers ER, Pringle KG (2022):
Role of the prorenin receptor in endometrial cancer cell growth.
Oncotarget 13: 587-599

Patel NR, Rajan KC, Blanks AE, Li Y, Prieto MC, Meadows SM:
Endothelial cell polarity and extracellular matrix composition require functional ATP6AP2 during developmental and pathological angiogenesis.
JCI Insight 2022 Aug 23 [epub]

Sato S, Hirose T, Ohba K, Watanabe F, Watanabe T, Minato K, Endo A, Ito H, Mori T, Takahashi K:
(Pro)renin receptor and insulin signaling regulate cell proliferation in MCF-7 breast cancer cells.
J Biochem 2022 Sep 7 [epub]

Ouyang X, Xu C:
Targeting the (pro)renin receptor in cancers: from signaling to pathophysiological effects.
J Cancer Res Clin Oncol 2022 Sep 25 [epub]  

Dehner CA, Schroeder MC, Lyu Y, Bell R, Borcherding DC, Moon T, Hirbe A, Chrisinger JSA:
Molecular characterization of multifocal granular cell tumors.
Am J Surg Pathol 2022 Nov 14 [epub]

Wang J, Ding Y, Li D, Zhu N, Nishiyama A, Yuan Y (2023):
(Pro)renin receptor promotes colorectal cancer progression through inhibiting the NEDD4L-mediated Wnt3 ubiquitination and modulating gut microbiota.
Cell Commun Signal 21: 2.

Fujimori T, Shibayama Y, Kanda T, Suzuki K, Ogawa D, Ishikawa R, Kadota K, Matsunaga T, Tamiya T, Nishiyama A, Miyake K (2023):
Effects of a monoclonal antibody against (pro)renin receptor on gliomagenesis.
Sci Rep 13: 808.

Taguchi T, Kimura K, Suzuki A, Fujishima R, Shimizu N, Hoshiyama A, Masaki T, Inoue M, Kato Y, Satomi T, Takano K, Imada T, Sasaki S, Miyatsuka T. (2023):
ATP6AP2 is robustly expressed in pancreatic β cells and neuroendocrine tumors, and plays a role in maintaining cellular viability.
Sci Rep 13: 9260.

Mohammad AH, Couture F, Gamache I, Chen O, El-Assaad W, Abdel-Malak N, Kwiatkowska A, Muller W, Day R, Teodoro JG (2023):
Cleavage of the V-ATPase associated prorenin receptor is mediated by PACE4 and is essential for growth of prostate cancer cells.
PLoS One 18: e0288622.

Warren SJ, Alomari AK:
Utility of sequencing for ATP6AP1 and ATP6AP2 to distinguish between atypical granular cell tumor with junctional component and melanoma.
J Cutan Pathol 2023 Aug 11 [epub]

Li W, Kawaguchi K, Tanaka S, He C, Maeshima Y, Suzuki E, Toi M (2023):
Cellular senescence triggers intracellular acidification and lysosomal pH alkalinized via ATP6AP2 attenuation in breast cancer cells.
Commun Biol 6: 1147.

Aliakbarian M, Ferns GA, Mohamadzadeh Shabestari M, Ahmadzadeh AM, Abdollahzade A, Rahimi H, Khodashahi R, Arjmand MH:
Elucidating the role of pro-renin receptors in pancreatic ductal adenocarcinoma progression: A novel therapeutic target in cancer therapy.
Curr Cancer Drug Targets 2024 Jan 25 [epub]  

Lozinski M, Lumbers ER, Bowden NA, Martin JH, Fay MF, Pringle KG, Tooney PA (2024):
Upregulation of the renin-angiotensin system is associated with patient survival and the tumour microenvironment in glioblastoma.
Cells 13: 634.

(4) Discovery of RERBs

Schrezenmeier E, Zollmann FS, Seidel K, Böhm C, Schmerbach K, Kroh M, Kirsch S, Klare S, Bernhard S, Kappert K, Goldin-Lang P, Skuballa W, Unger T, Funke-Kaiser H (2012): 
Moderate correlations of in vitro versus in vivo pharmacokinetics questioning the need of early microsomal stability testing.
Pharmacology 90: 307-315 

Abbas YM, Wu D, Bueler SA, Robinson CV, Rubinstein JL (2020):
Structure of V-ATPase from the mammalian brain.
Science 367: 1240-1246 

Rahman A, Matsuyama M, Ebihara A, Shibayama Y, Hasan AU, Nakagami H, Suzuki F, Sun J, Kobayashi T, Hayashi H, Nakano D, Kobara H, Masaki T, Nishiyama A:
Antiproliferative effects of monoclonal antibodies against (pro)renin receptor in pancreatic ductal adenocarcinoma.
Mol Cancer Ther 2020 Jul 15 [epub] 

Ebihara A, Sugihara D, Matsuyama M, Suzuki-Nakagawa C, Nabi AHMN, Nakagawa T, Nishiyama A, Suzuki F: Mapping the protein binding site of the (pro)renin receptor using in silico 3D structural analysis.
Hypertens Res 2022 Dec 9 [epub]

Funke-Kaiser H, Unger T:
The (pro)renin receptor as a pharmacological target in cardiorenal diseases.
Hypertens Res 2023 Sep 4 [epub]  

Funke-Kaiser, H., Unger, T.:
The (pro)renin receptor - A regulatory nodal point in disease networks.
Curr Drug Targets 2023 October 25 [epub]  

Fang H, Lin D, Li X, Wang L, Yang T (2023):
Therapeutic potential of Ganoderma lucidum polysaccharide peptide in Doxorubicin-induced nephropathy: modulation of renin-angiotensin system and proteinuria.
Front Pharmacol 14: 1287908.

Fang H, Li X, Lin D, Wang L, Yang T, Yang B (2023):
Inhibition of intrarenal PRR-RAS pathway by Ganoderma lucidum polysaccharide peptides in proteinuric nephropathy.
Int J Biol Macromol 253: 127336.

(5) Common mechanism approach - one target for multiple indications

Hoshijima M, Chien KR (2002):
Mixed signals in heart failure: cancer rules.
J Clin Invest 109: 849-855   

Nielsch U, Schäfer S, Wild H, Busch A (2007):
One target-multiple indications: a call for an integrated common mechanisms strategy.
Drug Discov Today 12: 1025-1031   

Blankesteijn WM, van de Schans VA, ter Horst P, Smits JF (2008):
The Wnt/frizzled/GSK-3 beta pathway: a novel therapeutic target for cardiac hypertrophy.
Trends Pharmacol Sci 29: 175-180   

Dai C, Stolz DB, Kiss LP, Monga SP, Holzman LB, Liu Y (2009):
Wnt/beta-catenin signaling promotes podocyte dysfunction and albuminuria.
J Am Soc Nephrol 20: 1997-2008 

Zaade D, Schmitz J, Benke E, Klare S, Seidel K, Kirsch S, Goldin-Lang P, Zollmann F, Unger T, Funke-Kaiser H (2013):  
Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.
Plos One 8: e57674

Li C, Siragy HM (2014):
High glucose induces podocyte injury via anhanced (pro)renin receptor-Wnt-beta-catenin-snail signaling pathway.
PLoS One 9: e89233

Springer J, Tschirner A, Haghikia A, von Haehling S, Lal H, Grzesiak A, Kaschina E, Palus S, Pötsch M, von Websky K, Hocher B, Latouche C, Jaisser F, Morawietz L, Coats AJ, Beadle J, Argiles JM, Thum T, Földes G, Doehner W, Hilfiker-Kleiner D, Force T, Anker SD (2014):
Prevention of liver cancer cachexia-induced cardiac wasting and heart failure.
Eur Heart J 35: 932-941

Zhou L, Li Y, Hao S, Zhou D Tan RJ, Nie J, Hou FF, Kahn M, Liu Y (2014):
Multiple genes of the renin-angiotensin system are novel targets of Wnt/beta-catenin signaling.
J Am Soc Nephrol 26: 107-20 

Van der Heiden MG, Cantley LC, Thompson CB (2009):
Understanding the Warburg effect: the metabolic requirements of cell proliferation.
Science 324: 1029-1033  

Zhao Y, Butler EB, Tan M (2013):
Targeting cellular metabolism to improve cancer. 
Cell Death Dis 4: e532  

Zhou L, Liu Y (2015):
Wnt/beta-catenin signalling and podocyte dysfunction in proteinuric kidney. 
Nat Rev Nephrol 11: 535-45  

Ichihara A, Yatabe MS (2019):
The (pro)renin receptor in health and disease.
Nat Rev Nephrol 2019 Jun 4 [epub]  

(6) Further indications

Hirano Y, Takeuchi H, Suda K, Hagiwara T, Miyasho T, Kawamura Y, Yamada S, Oyama T, Takahashi T, Wada N, Saikawa Y, Ichihara A, Kitagawa Y (2014):
(Pro)renin receptor blocker improves survival of rats with sepsis.
J Surg Res 186: 269-277   

Ono M, Sakao Y, Tsuji T, Ohashi N, Yasuda H, Nishiyama A, Fujigaki Y, Kato A (2014):
Role of intrarenal (pro)renin receptor in ischemic acute kidney injury in rats.
Clin Exp Nephrol 19: 185-96  

Chandel N, Ayasolla K, Lan X, Rai P, Mikulak J, Husain M, Malhotra A, McGowan J, Singhal PC (2014):
Renin modulates HIV replication in T cells.
J Leukoc Biol 96: 601-609 

Li W, Sullivan MN, Zhang S, Worker CJ, Xiong Z, Speth RC, Feng Y (2015):
Intracerebroventricular infusion of the (pro)renin receptor antagonist PRO20 attenuates deoxycorticosterone acetate-salt-induced hypertension.
Hypertension 65: 352-61  

Ishii K, Takeuchi H, Fukunaga K, Hirano Y, Suda K, Hagiwara T, Miyasho T, Yamada S, Nakamura R, Takahashi T, Wada N, Kawakubo H, Saikawa Y, Omori T, Betsuyaku T, Ichihara A, Kitagawa Y (2015): 
Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin receptor blockade.
Exp Lung Res 41: 199-207

Haque R, Iuvone, PM, He L, Choi KSC, Ngo A, Gokhale S, AseemM, Park D (2017):
The MicroRNA-21 signaling pathway is involved in prorenin receptor (PRR)-induced VEGF expression in ARPE-19 cells under a hyperglycemic condition.
Mol Vis 23: 251-262 

Kanda A, Ishizuka ET, Shibata A, Matsumoto T, Toyofuku H, Noda K, Namba K, Ishida S (2017):
A novel single-strand RNAi therapeutic agent targeting the (pro)renin receptor suppresses ocular Inflammation.
Mol Ther Nucleic Acids 7: 116-126 

Yoshida N, Endo J, Kinouchi K, Kitakata H, Moriyama H, Kataoka M, Yamamoto T, Shirakawa K, Morimoto S, Nishiyama A, Hashiguchi A, Higuchi I, Fukuda K, Ichihara A, Sano M (2019):
(Pro)renin receptor accelerates development of sarcopenia via activation of Wnt/YAP signaling axis.
Aging Cell 8: e12991.

Hsieh YC, Lee KC, Lei HJ, Lan KH, Huo TI, Lin YT, Chan CC, Schnabl B, Huang YH, Hou MC, Lin HC:
(Pro)renin receptor knockdown attenuates liver fibrosis through inactivation of ERK/TGF-β1/SMAD3 pathway.
Cell Mol Gastroenterol Hepatol  2021 Jun 1 [epub]

Lopez-Lopez A, Villar-Cheda B, Quijano A, Garrido-Gil P, Garcia-Garrote M, Diaz-Ruiz C, Munoz A, Labandeira-Garcia JL (2021):
NADPH-oxidase, Rho-kinase and autophagy mediate the (pro)renin-induced pro-inflammatory microglial response and enhancement of dopaminergic neuron death.
Antioxidants (Basel) 10: 1340.

Hu J, Tan Y, Chen Y, Mo S, Hekking B, Su J, Pu M, Lu A, Symons JD, Yang T:
Role of (pro)renin receptor in cyclosporin A-induced nephropathy.
Am J Physiol Renal Physiol 2022 Jan 24 [epub]