SIRT7 deficiency in hepatic cell mediates PAI-1 secretion, activating hepatic stellate cell and promoting liver fibrosis
YU Tingzi, DING Cong, TANG Yongyi, LI Zhuan
Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha 410013, China
Abstract：Background The population affected by liver fibrosis is extensive, yet treatment options are lacking. SIRT7, a member of the sirtuin family of histone deacetylases, is involved in various physiological processes such as cellular aging, metabolism, and inflammatory responses. It has been reported that SIRT7 plays crucial roles in many liver diseases, including hepatocellular carcinoma and non-alcoholic fatty liver disease, but its function in liver fibrosis remains unclear. Methods A liver fibrosis model was established by alternate-day intraperitoneal injection of CCl4 in both wild-type mice and hepatocyte SIRT7 knockout mice, followed by assessment of injury and fibrosis phenotypes. Subsequently, primary cells were used for in vitro co-culture experiments, combined with array analysis to further determine the mediators of hepatic stellate cell (HSC) activation affected by SIRT7 deficiency. Conclusion SIRT7 deficiency exacerbated CCl4-induced liver injury and fibrosis phenotypes. Further research indicated that SIRT7 deficiency mediated differential activation of hepatic stellate cells (HSCs) through hepatocyte PAI-1 secretion, thereby promoting liver fibrosis. Our results suggested that SIRT7-mediated signaling plays a significant role in liver injury and fibrosis, and therapeutic targeting SIRT7 may be an effective approach for treating liver fibrosis.
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2024, Vol. 21 
