GRK2/ß-arrestin mediates arginine vasopressin-induced cardiac fibroblast proliferation.

Authors: Chen, Yunxuan  Xu, Feifei  Zhang, Lingling  Wang, Xiaojun  Wang, Yifan  Woo, Anthony Yiu-Ho  Zhu, Weizhong 
Citation: Chen Y, etal., Clin Exp Pharmacol Physiol. 2017 Feb;44(2):285-293. doi: 10.1111/1440-1681.12696.
Pubmed: (View Article at PubMed) PMID:27862165
DOI: Full-text: DOI:10.1111/1440-1681.12696

Cardiac fibrosis is a pathological feature commonly found in hearts exposed to haemodynamic orneurohormonal stress. Elevated levels of arginine vasopressin (AVP) are closely associated with the progression of heart failure and could be an underlying cause of cardiac fibrosis. The aim of this study is to characterize the effect of AVP on neonatal rat cardiac fibroblasts (NRCFs) and to illustrate its signalling mechanism. The proliferative effect of AVP was assessed by methylthiazolyldiphenyl-tetrazolium assay and 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, and the amounts of cellular signalling proteins α-smooth muscle actin (α-SMA), matrix metalloproteinase (MMP) 2, MMP9, and phosphorylated ERK1/2were determined by western blotting. AVP, in a time- and concentration-dependent manner, promoted NRCF proliferation and the expression of MMP2 and MMP9. Inhibition of G protein-coupled receptor kinase2 (GRK2) by the inhibitory peptide GRK2-Ct or knock-down of GRK2 suppressed AVP-induced BrdU incorporation and the expression of MMP2 and α-SMA in NRCFs. Moreover, shRNA-mediated silencing of ß-arrestin1 or ß-arrestin 2 abolished AVP-induced BrdU incorporation and MMP2 expression. AVP-induced NRCF proliferation depended on the phosphorylation of ERK1/2, and inhibition of GRK2 or silencing of ß-arrestins blocked AVP-induced ERK1/2phosphorylation. The effects of AVP on NRCF proliferation and α-SMA expression were blocked by SR45059, a vasopressin receptor type1A (V1AR) selective antagonist. In conclusion, AVP promotes NRCF proliferation through V1AR-mediated GRK2/ß-arrestin/ERK1/2signalling.

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CRRD Object Information
CRRD ID: 13513991
Created: 2018-03-20
Species: All species
Last Modified: 2018-03-20
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.