Aliskiren reduces the release of soluble (pro)renin receptor from human umbilical vein endothelial cells

  • Authors:
    • Shinji Yamashita
    • Kazal Boron Biswas
    • A.H.M. Nurun Nabi
    • Tsutomu Nakagawa
    • Fumiaki Suzuki
    • Akio Ebihara
  • View Affiliations

  • Published online on: July 5, 2018     https://doi.org/10.3892/br.2018.1124
  • Pages: 247-252
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

(Pro)renin receptor [(P)RR] has been implicated in diverse biological processes through binding to its ligands, which include renin, prorenin, Wnt signaling molecules and subunits of vascular H+‑ATPase. Recent studies have reported that (P)RR is implicated in pathophysiological conditions including retinopathy and pancreatic ductal adenocarcinoma, and the soluble form of this receptor [s(P)RR] is considered as a useful biomarker for diseases. The present study examined the effect of aliskiren, the first orally active direct renin inhibitor, on the protein levels of (P)RR using cultured human umbilical vein endothelial cells (HUVECs). The cells were treated with or without aliskiren (10 nM) at 37˚C for different durations (0, 8, 16 and 24 h). Aliskiren‑treated HUVECs exhibited reduced proliferation compared with those treated without the drug. Furthermore, aliskiren treatment decreased not only the level of exogenous prorenin that bound to the membranes of HUVECs, but also the renin activity derived from this binding activity. These results indicate that the quantity of full‑length (P)RR was reduced by aliskiren treatment, and furthermore, that the level of s(P)RR released from HUVECs was decreased with the treatment. Recent study has reported that s(P)RR exerted antidiuretic function. The current study suggests that the levels of s(P)RR, as a potential antidiuretic molecule and prospective disease biomarker, may be decreased during anti‑hypertensive treatments with aliskiren.

References

1 

Nguyen G, Delarue F, Burcklé C, Bouzhir L, Giller T and Sraer JD: Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest. 109:1417–1427. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Krop M, Lu X, Danser AH and Meima ME: The (pro)renin receptor. A decade of research: What have we learned? Pflugers Arch. 465:87–97. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Nabi AHMN, Biswas KB, Ebihara A, Nakagawa T and Suzuki F: Renin angiotensin system in the context of renin, prorenin, and the (pro)renin receptor. Rev Agric Sci. 1:43–60. 2013.

4 

Kinouchi K, Ichihara A, Sano M, Sun-Wada GH, Wada Y, Kurauchi-Mito A, Bokuda K, Narita T, Oshima Y, Sakoda M, et al: The (pro)renin receptor/ATP6AP2 is essential for vacuolar H+-ATPase assembly in murine cardiomyocytes. Circ Res. 107:30–34. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Cruciat CM, Ohkawara B, Acebron SP, Karaulanov E, Reinhard C, Ingelfinger D, Boutros M and Niehrs C: Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling. Science. 327:459–463. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Kanda A, Noda K, Saito W and Ishida S: (Pro)renin receptor is associated with angiogenic activity in proliferative diabetic retinopathy. Diabetologia. 55:3104–3113. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Matavelli LC, Huang J and Siragy HM: (Pro)renin receptor contributes to diabetic nephropathy by enhancing renal inflammation. Clin Exp Pharmacol Physiol. 37:277–282. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Contrepas A, Walker J, Koulakoff A, Franek KJ, Qadri F, Giaume C, Corvol P, Schwartz CE and Nguyen G: A role of the (pro)renin receptor in neuronal cell differentiation. Am J Physiol Regul Integr Comp Physiol. 297:R250–R257. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Shibayama Y, Fujimori T, Nguyen G, Hirose T, Totsune K, Ichihara A, Kitada K, Nakano D, Kobori H, Kohno M, et al: (Pro)renin receptor is crucial for Wnt/β-catenin-dependent genesis of pancreatic ductal adenocarcinoma. Sci Rep. 5:88542015. View Article : Google Scholar : PubMed/NCBI

10 

Ludwig J, Kerscher S, Brandt U, Pfeiffer K, Getlawi F, Apps DK and Schägger H: Identification and characterization of a novel 9.2-kDa membrane sector-associated protein of vacuolar proton-ATPase from chromaffin granules. J Biol Chem. 273:10939–10947. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Cousin C, Bracquart D, Contrepas A, Corvol P, Muller L and Nguyen G: Soluble form of the (pro)renin receptor generated by intracellular cleavage by furin is secreted in plasma. Hypertension. 53:1077–1082. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Nakagawa T, Suzuki-Nakagawa C, Watanabe A, Asami E, Matsumoto M, Nakano M, Ebihara A, Uddin MN and Suzuki F: Site-1 protease is required for the generation of soluble (pro)renin receptor. J Biochem. 161:369–379. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Gonzalez AA, Lara LS, Luffman C, Seth DM and Prieto MC: Soluble form of the (pro)renin receptor is augmented in the collecting duct and urine of chronic angiotensin II-dependent hypertensive rats. Hypertension. 57:859–864. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Morimoto S, Ando T, Niiyama M, Seki Y, Yoshida N, Watanabe D, Kawakami-Mori F, Kobori H, Nishiyama A and Ichihara A: Serum soluble (pro)renin receptor levels in patients with essential hypertension. Hypertens Res. 37:642–648. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Lu X, Wang F, Xu C, Soodvilai S, Peng K, Su J, Zhao L, Yang KT, Feng Y, Zhou SF, et al: Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor. Proc Natl Acad Sci USA. 113:E1898–E1906. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Wood JM, Maibaum J, Rahuel J, Grütter MG, Cohen NC, Rasetti V, Rüger H, Göschke R, Stutz S, Fuhrer W, et al: Structure-based design of aliskiren, a novel orally effective renin inhibitor. Biochem Biophys Res Commun. 308:698–705. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Pantzaris ND, Karanikolas E, Tsiotsios K and Velissaris D: Renin inhibition with aliskiren: A decade of clinical experience. J Clin Med. 6:62017. View Article : Google Scholar

18 

Feldman DL, Jin L, Xuan H, Contrepas A, Zhou Y, Webb RL, Mueller DN, Feldt S, Cumin F, Maniara W, et al: Effects of aliskiren on blood pressure, albuminuria, and (pro)renin receptor expression in diabetic TG(mRen-2)27 rats. Hypertension. 52:130–136. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Ferri N, Greco CM, Maiocchi G and Corsini A: Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells. J Renin Angiotensin Aldosterone Syst. 12:469–474. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Biswas KB, Nabi AN, Arai Y, Nakagawa T, Ebihara A, Ichihara A, Inagami T and Suzuki F: Qualitative and quantitative analyses of (pro)renin receptor in the medium of cultured human umbilical vein endothelial cells. Hypertens Res. 34:735–739. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Nachman RL and Jaffe EA: Endothelial cell culture: Beginnings of modern vascular biology. J Clin Invest. 114:1037–1040. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Nasir UM, Takahashi K, Nagai T, Nakagawa T, Suzuki F and Nakamura Y: Two peaks in pH dependence of renin-angiotensinogen reaction. Biosci Biotechnol Biochem. 62:338–340. 1998. View Article : Google Scholar : PubMed/NCBI

23 

Suzuki F, Hayakawa M, Nakagawa T, Nasir UM, Ebihara A, Iwasawa A, Ishida Y, Nakamura Y and Murakami K: Human prorenin has ‘gate and handle’ regions for its non-proteolytic activation. J Biol Chem. 278:22217–22222. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Danser AH and Deinum J: Renin, prorenin and the putative (pro)renin receptor. Hypertension. 46:1069–1076. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Nagase M, Suzuki F, Sawai Y, Orihashi T, Inui Y, Nakagawa T and Nakamura Y: Purification and some properties of recombinant sheep angiotensinogen expressed in Chinese hamster ovary cells. Biomed Research Tokyo. 18:439–443. 1997. View Article : Google Scholar

26 

Ebihara A, Nasir UM, Yoshida S, Kondou T, Nakagawa T, Fukamizu A, Suzuki F, Nakamura Y and Murakami K: Sialic acid residue of ovine angiotensinogen does not affect the reactivity to human renin. Biomed Research Tokyo. 21:105–109. 2000. View Article : Google Scholar

27 

Suzuki F, Yamashita S, Takahashi A, Ito M, Miyazaki S, Nagata Y and Nakamura Y: Highly sensitive microplate ELISA for angiotensin I using 3,3′5,5′tetramethylbenzidine. Clin Exp Hypertens. A12:83–95. 1990.

28 

Nabi AH, Biswas KB, Nakagawa T, Ichihara A, Inagami T and Suzuki F: Prorenin has high affinity multiple binding sites for (pro)renin receptor. Biochim Biophys Acta. 1794:1838–1847. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Ku HH: Notes Use Propag Error Formulas. J Res Natl Bur Stand. 70C:263–273. 1966.

30 

Nabi AH, Kageshima A, Uddin MN, Nakagawa T, Park EY and Suzuki F: Binding properties of rat prorenin and renin to the recombinant rat renin/prorenin receptor prepared by a baculovirus expression system. Int J Mol Med. 18:483–488. 2006.PubMed/NCBI

31 

Nurun NA, Uddin NM, Nakagawa T, Iwata H, Ichihara A, Inagami T and Suzuki F: Role of ‘handle’ region of prorenin prosegment in the non-proteolytic activation of prorenin by binding to membrane anchored (pro)renin receptor. Front Biosci. 12:4810–4817. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

September 2018
Volume 9 Issue 3

Print ISSN: 2049-9434
Online ISSN:2049-9442

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Yamashita, S., Biswas, K.B., Nabi, A.N., Nakagawa, T., Suzuki, F., & Ebihara, A. (2018). Aliskiren reduces the release of soluble (pro)renin receptor from human umbilical vein endothelial cells. Biomedical Reports, 9, 247-252. https://doi.org/10.3892/br.2018.1124
MLA
Yamashita, S., Biswas, K. B., Nabi, A. N., Nakagawa, T., Suzuki, F., Ebihara, A."Aliskiren reduces the release of soluble (pro)renin receptor from human umbilical vein endothelial cells". Biomedical Reports 9.3 (2018): 247-252.
Chicago
Yamashita, S., Biswas, K. B., Nabi, A. N., Nakagawa, T., Suzuki, F., Ebihara, A."Aliskiren reduces the release of soluble (pro)renin receptor from human umbilical vein endothelial cells". Biomedical Reports 9, no. 3 (2018): 247-252. https://doi.org/10.3892/br.2018.1124