Mechanisms of the TGF-β1/Smad3-signaling pathway in gender differences in alcoholic liver fibrosis

Xiao-Min Hong1, Sanqiang Li1, Rui Luo1, Mei Yang1, Jianhui Wu2, Shuning Chen3, Siyu Zhu1
1The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, 471003, People’s Republic of China
2Henan Center for Engineering and Technology Research On Prevention and Treatment of Liver Diseases, Luoyang, 471003, People’s Republic of China
3Pharmaceutical Science, Monash University, Melbourne, Australia

Tóm tắt

Abstract

The TGF-β1/Smad3-signaling pathway and gender differences were investigated in alcoholic liver fibrosis. Mice were divided into female normal, female model, male normal, and male model groups. Liver injury and fibrosis were assessed using histopathology and serology. Western blotting was performed to analyze the expression of relevant factors. HSC-T6 cells were divided into estradiol + saline, estradiol + ethanol, testosterone + saline, and testosterone + ethanol groups, and similar assessments were conducted in vitro. Compared with the female model group, the male model group exhibited significantly increased GPT, GOT, TNF-α, IL-6, and testosterone levels, fibrosis rate, and TGF-β1, Smad3, and PCNA expression, and significantly decreased estradiol levels and Caspase-3 expression. The apoptosis rate was higher in the estradiol + ethanol group than in the testosterone + ethanol group, although the testosterone + ethanol group exhibited significantly increased TNF-α, IL-6, Collagen-I, α-SMA, TGF-β1, Smad3, and PCNA expression, and significantly decreased Caspase-3 expression. Alcoholic liver fibrosis showed significant gender differences associated with the TGF-β1/Smad3-signaling pathway.

Từ khóa


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