title: [Angiotensin (1-7) inhibits angiotensin II-stimulated expression of connective tissue growth factor mRNA in hepatic stellate cells].
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.
authors.affiliation: Department of Emergency, the South Medical University, Guangzhou, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Mao-liang
authors.initials: ML
authors.lastname: Huang
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.forename: Wen-yong
authors.initials: WY
authors.lastname: Zhang
authors.forename: Zuo-wei
authors.initials: ZW
authors.lastname: Ning
authors.forename: Ying
authors.initials: Y
authors.lastname: Meng
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: C526317:CCN2 protein, human; D010446:Peptide Fragments; D012333:RNA, Messenger; D000804:Angiotensin II; C066737:RHOA protein, human; D055513:Connective Tissue Growth Factor; D000803:Angiotensin I; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; C118790:angiotensin I (1-7)