Exogenous angiotensin (1-7) directly inhibits epithelial-mesenchymal transformation induced by transforming growth factor-ß1 in alveolar epithelial cells.
Biomed Pharmacother
; 117: 109193, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31387171
ABSTRACT
Accumulating evidence indicates that angiotensin (1-7) [Ang-(1-7)] protects against idiopathic pulmonary fibrosis (IPF) in animal experiments. However, whether Ang-(1-7) effectively inhibits epithelial-mesenchymal transition (EMT) induced by transforming growth factor-ß1 (TGF-ß1) remains unclear. The aim of this study is to examine the eï¬ ;ects of Ang-(1-7) on TGF-ß1-induced EMT in human alveolar epithelial cells. We found that angiotensin-converting enzyme 2 (ACE2) /Ang-(1-7)/MasR were decreased in the lungs of mice with IPF induced by bleomycin, and were negatively correlated with Tgfb1 mRNA expression. In vitro, our data showed that exogenous Ang-(1-7) restored the expression of E-cadherin and decreased the expressions of α-SMA and Vimentin induced by TGF-ß1 in A549 cells. Ang-(1-7) also reduced TGF-ß1-induced migration and synthesis of the extracellular matrix, such as collagen â
and collagen â
¢. Mechanistically, we observed that Ang-(1-7) directly inhibited TGF-ß1-induced phosphorylation of Smad2 and Smad3, and suppressed the expression of the downstream target gene of TGF-ß1-Smad signaling, including ZEB1, ZEB2, TWIST, and SNAIL1. Additionally, phosphorylation of mTOR induced by TGF-ß1 also been suppressed by Ang-(1-7) treatment in A549 cells. Interestingly, we found that TGF-ß1 strongly suppressed the expression of ACE2 in A549 cells through inhibiting SIRT1. In conclusion, our findings indicate that Ang-(1-7) directly inhibits TGF-ß1-induced EMT in alveolar epithelial cells via disruption of TGF-ß1-Smad signaling pathway, contributing to the protective effect against IPF.
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Assunto principal:
Fragmentos de Peptídeos
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Angiotensina I
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Fator de Crescimento Transformador beta1
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Células Epiteliais Alveolares
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Transição Epitelial-Mesenquimal
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article