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Abstract
Liver fibrosis is a chronic liver disease with progressive wound healing reaction caused by liver injury. Currently, there is no FDA approved drugs for liver fibrosis. Human adipose mesenchymal stem cells (hADSCs) have shown remarkable therapeutic effects in liver diseases. However, few studies have evaluated the therapeutic role of hADSCs in liver fibrosis, and the detailed mechanism of action is unknown. Here, we investigated the in vitro and in vivo anti-fibrosis efficacy of hADSCs and identified important metabolic changes and detailed mechanisms through transcriptomic and metabolomic analyses. We found that hADSCs could inhibit the proliferation of activated hepatic stellate cells (HSCs), promote their apoptosis, and effectively inhibit the expression of pro-fibrotic protein. It can significantly reduce collagen deposition and liver injury, improve liver function and alleviate liver inflammation in cirrhotic mouse models. In addition, transcriptome analysis revealed that the key mechanism of hADSCs against liver fibrosis is the regulation of AGE-RAGE signaling pathway. Metabolic analysis showed that hADSCs influenced changes of metabolites in lipid metabolism. Therefore, our study shows that hADSCs could reduce the activation of hepatic stellate cells and inhibit the progression of liver fibrosis, which has important potential in the treatment of liver fibrosis as well as other refractory chronic liver diseases.
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Details
1 Southern Medical University, Nanfang Hospital, Guangzhou, People’s Republic of China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471); Wuhan Fourth Hospital, Department of Hepatobiliary-Pancreatic and Hernia Surgery, Wuhan, People’s Republic of China (GRID:grid.501233.6) (ISNI:0000 0004 1797 7379)
2 Wuhan Fourth Hospital, Department of Hepatobiliary-Pancreatic and Hernia Surgery, Wuhan, People’s Republic of China (GRID:grid.501233.6) (ISNI:0000 0004 1797 7379)
3 Wuhan Fourth Hospital, Department of Trauma and Orthopedics, Wuhan, People’s Republic of China (GRID:grid.501233.6) (ISNI:0000 0004 1797 7379)
4 Wuhan Fourth Hospital, Department of Gastroenterology Surgery, Wuhan, People’s Republic of China (GRID:grid.501233.6) (ISNI:0000 0004 1797 7379)
5 Huazhong University of Science and Technology, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Hepatic Surgery Center, Tongji Medical College, Tongji Hospital, Wuhan, People’s Republic of China (GRID:grid.33199.31) (ISNI:0000 0004 0368 7223)
6 Southern Medical University, Nanfang Hospital, Guangzhou, People’s Republic of China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471); Southern Medical University, Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Guangzhou, People’s Republic of China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471)