Taurine protected As2O3-induced the activation of hepatic stellate cells through inhibiting PPARα-autophagy pathway. (25th February 2019)

• Record Type: Journal Article
• Authors: Wang, Zhidong; Tao, Ye; Qiu, Tianming; Yao, Xiaofeng; Jiang, Liping; Wang, Ningning; Wei, Sen; Jia, Xue; Pei, Pei; Yang, Guang; Liu, Xiaofang; Liu, Shuang; Sun, Xiance
• Is Part Of: Chemico-biological interactions. Volume 300(2019)
• Page Start: 123
• Page End: 130
• Publication Date: 2019-02-25
• Subjects: Hepatic stellate cells -- Arsenic -- Fibrosis -- Autophagy -- PPARα; HSCs hepatic stellate cells -- Tau taurine -- PPARα peroxisome proliferator activated receptors alpha -- NAFLD Non-alcoholic fatty liver disease -- PDGF-BB platelet derived growth factor BB -- PPARs peroxisome proliferator activated receptors -- FA fatty acid -- 3-MA 3-methyladenine; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2019.01.019
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: The activation of hepatic stellate cells (HSCs) is a key event in the development of hepatic fibrosis caused by arsenic. However, it is unclear how arsenic induces the activation of HSCs. In the present study, we found that arsenic trioxide (As2 O3 ) induced liver tissue damage, stimulated autophagy and HSCs activation, and increased collagen accumulation in the liver of mice. Supplemented with taurine (Tau) attenuated the changes mentioned above caused by As2 O3 . In human hepatic stellate cell line LX-2 cells, we found that As2 O3 -induced activation of HSCs was autophagy-dependent, and we found that peroxisome proliferator activated receptors alpha (PPARα) played an important role in arsenic-induced HSCs activation. In addition, inhibiting autophagy and PPARα alleviated the activation of HSCs and lipid droplet loss induced by As2 O3 . Moreover, we found that Tau alleviated As2 O3 -induced elevation of autophagy and PPARα expression, and activation of the HSCs. Our results indicated that autophagy was regulated by PPARα and was involved in lipid droplet loss during the activation of HSCs. Tau alleviated As2 O3 -induced HSCs activation by inhibiting the PPARα/autophagy pathway. These findings give an innovative insight into the association of PPARα, autophagy, the activation of HSCs and hepatic fibrosis induced by As2 O3 . Highlights: As2 O3 -induced the activation of hepatic stellate cells was autophagy-dependent. PPARα played an important role in arsenic-induced HSCs activation. Taurine decreased the level of autophagy, and inhibited the activity of hepatic stellate cells.