Pepstatin Pr show anti-fibrosis effect related to YAP-TGFβ-Smad pathway
10.16438/j.0513-4870.2018-0705
- VernacularTitle:Pepstatin Pr通过YAP-TGFβ-Smad通路发挥体外抗肝纤维化作用
- Author:
Wei-xiao NIU
1
;
Ming-hua CHEN
1
;
Na ZHANG
1
;
Mao-xu GE
1
;
Yun-yang BAO
1
;
Shu-yi SI
1
;
Rong-guang SHAO
1
;
Hong-wei HE
1
Author Information
1. Inititute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
liver fibrosis;
cathepsin D;
TGFβ-Smad;
YAP/TAZ
- From:
Acta Pharmaceutica Sinica
2019;54(1):89-94
- CountryChina
- Language:Chinese
-
Abstract:
Liver fibrosis is a tissue repair compensatory response to liver injury caused by various chronic factors, ultimately leading to liver cirrhosis, liver failure and even hepatocellular carcinoma. Abnormal activation of hepatic stellate cells is the cellular basis of liver fibrosis development. Pepstatin Pr, the derivative of pepstatin A, was isolated from Streptomyces sp. CPCC 202950. Our purpose was to investigate the anti-fibrotic activity of pepstatin Pr and explore its molecular mechanism. Hepatic stellate cell LX-2 was stimulated by TGFβ1 and sub- sequently treated with pepstatin Pr. Its cytotoxicity was detected by sulforhodamine B (SRB) assay. The expression of COL1A1, α-SMA and cathepsin D, signaling proteins TGFβ, Smad and YAP/TAZ were detected by Western blot or real-time PCR. The results showed that pepstatin Pr was not cytotoxic to LX-2 cells. And pepstatin Pr significantly reduced the mRNA and protein expression of COL1A1 and α-SMA, which are important liver fibrosis markers. Pepstatin Pr also repressed the protein expression level of cathepsin D, TGFβ1, YAP/TAZ, the phospholation level of Smad2, and YAP nuclear translocation. In conclusion, pepstatin Pr exhibits anti-fibrotic effects in TGFβ1-stimulaed LX-2 cells by mediating YAP-TGFβ-Smad pathway.
