Angiotensin (1-7) inhibits angiotensin II-stimulated expression of connective tissue growth factor mRNA in hepatic stellate cells.
10.3760/cma.j.issn.1007-3418.2012.06.016
- Author:
Xu LI
1
;
Mao-liang HUANG
;
Shan HUANG
;
Wen-yong ZHANG
;
Zuo-wei NING
;
Ying MENG
Author Information
1. Department of Emergency, the South Medical University, Guangzhou, China.
- Publication Type:Journal Article
- MeSH:
Angiotensin I;
pharmacology;
Angiotensin II;
pharmacology;
Cells, Cultured;
Connective Tissue Growth Factor;
metabolism;
Hepatic Stellate Cells;
drug effects;
metabolism;
Humans;
Peptide Fragments;
pharmacology;
RNA, Messenger;
genetics;
Signal Transduction;
rho-Associated Kinases;
metabolism;
rhoA GTP-Binding Protein;
metabolism
- From:
Chinese Journal of Hepatology
2012;20(6):458-462
- CountryChina
- Language:Chinese
-
Abstract:
To explore the angiotensin peptide [Ang (1-7)]-mediated inhibition of Ang II in human hepatic stellate cells (HSCs) and determine the involvement of the ACE2-Ang (1-7)-Mas axis. The human HSC line, LX2, was used in all experiments, and divided into control (unstimulated) and Ang II-stimulated (10-6 mol/L) groups. The Ang II-stimulated cells were further divided among several pre-treatment (prior to Ang II) groups: ROCK-inhibited (Y27632 blocking agent, 10-6 mol/L); irbesartan-inhibited (AT-1 receptor antagonist, 10-6 mol/L); and Mas receptor-inhibited (A779 Mas receptor antagonist, 10-6 mol/L). To explore the potential inhibitory effects of various Ang family members, the Ang II-stimulated and pre-treated LX2 cells were exposed to Ang (1-7) (10-6 mol/L) for 24 h. Western blot, reverse transcription-polymerase chain reaction (RT-PCR), and QuantiGene assay were used to assess changes in protein and mRNA expression levels of RhoA, ROCK, and connective tissue growth factor (CTGF). Compared with the control group, Ang II-stimulated cells showed significantly increased levels of RhoA protein (0.337+/-0.074 vs. 0.870+/-0.093), ROCK2 mRNA (0.747+/-0.061 vs. 0.368+/-0.023), and CTGF mRNA (0.262+/-0.007 vs. 0.578+/-0.028) (all, P less than 0.01). Pre-treatment with irbesartan or Y27632 eliminated these responses. Ang (1-7) inhibited the Ang II-stimulated up-regulation of RhoA, ROCK, and CTGF. Ang (1-7) can inhibit the Ang II-stimulated up-regulation of RhoA, ROCK and CTGF in hepatic stellate cells, indicating that the ACE2-Ang (1-7)-Mas axis, an important branch of the renin-Ang-aldosterone system is involved in the occurrence and development of liver fibrosis.
