Journal
JOURNAL OF HYPERTENSION
Volume 29, Issue 4, Pages 696-705Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0b013e328343c62b
Keywords
(pro) renin receptor; epidermal growth factor receptor; prorenin; vascular smooth muscle cell
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20590253]
- Japan Research Foundation for Clinical Pharmacology
- Kagawa University
- Grants-in-Aid for Scientific Research [20590253] Funding Source: KAKEN
Ask authors/readers for more resources
Background It is widely acknowledged that the (pro) renin receptor mediates angiotensin (Ang) II-dependent and Ang II-independent effects of prorenin. Method We examined the effect of prorenin on vascular smooth muscle cell (VSMC) signal transduction, proliferation, and hypertrophy. Results Recombinant rat prorenin dose-dependently increased extracellular signal-regulated kinase (ERK) 1/2 and Akt phosphorylation in rat VSMCs. Prorenin also significantly increased cell number, and [(3)H]-thymidine and [(3)H]-leucine incorporation, which were attenuated by pretreatment with inhibitors for ERK kinase and phosphatidylinositol 3 kinase. Prorenin was also found to stimulate epidermal growth factor (EGF) receptor and Src phosphorylation. Pretreatment of VSMCs with an EGF receptor tyrosine kinase inhibitor and a Src inhibitor significantly attenuated the prorenin-induced increase in ERK 1/2 and Akt phosphorylation, as well as DNA and protein synthesis. Prorenin-induced phosphorylation of the EGF receptor, ERK 1/2, and Akt, as well as DNA and protein synthesis were all blocked by (pro) renin receptor siRNA, but not by an Ang II type 1 receptor blocker, candesartan, nor an Ang-converting enzyme inhibitor, captopril. Conclusion These results reveal that prorenin directly stimulates VSMC proliferative and hypertrophic changes, dependent on the (pro) renin receptor, independent of Ang II. Furthermore, EGF receptor-mediated ERK 1/2 and Akt activation contributes to prorenin-dependent proliferative and hypertrophic effects in VSMCs. J Hypertens 29:696-705 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available