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Extracellular vesicles-derived miR-150-5p secreted by adipose-derived mesenchymal stem cells inhibits CXCL1 expression to attenuate hepatic fibrosis |
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| Authors: | Zhiyong Du Tianchong Wu Linsen Liu Biwei Luo Cuifeng Wei |
| Institution: | 1. Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, Guangzhou, China
The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China Contribution: Conceptualization (equal), Investigation (equal), Writing - original draft (equal);2. Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, Guangzhou, China The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China Contribution: Data curation (equal), Methodology (equal), Visualization (equal);3. Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, Guangzhou, China The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China Contribution: Formal analysis (equal), Validation (equal);4. Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, Guangzhou, China The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China Contribution: Project administration (equal), Supervision (equal);5. Department of Endocrinology, Jingmen First People’s Hospital, Jingmen, China |
| Abstract: | Hepatic fibrosis (HF) is involved in aggravated wound-healing response as chronic liver injury. Extracellular vesicles (EVs) carrying microRNA (miR) have been reported as therapeutic targets for liver diseases. In this study, we set out to explore whether adipose-derived mesenchymal stem cells (ADMSCs)-derived EVs containing miR-150-5p affect the progression of HF. Carbon tetrachloride (CCl4) was firstly used to induce HF mouse models in C57BL/6J mice, and activation of hepatic stellate cells (HSCs) was achieved using transforming growth factor β (TGF-β). EVs were then isolated from ADMSCs and co-cultured with HSCs. The relationship between miR-150-5p and CXCL1 was identified using dual luciferase gene reporter assay. Following loss- and gain-function experimentation, HSC proliferation was examined by MTT assay, and levels of fibrosis-, HSC activation- and apoptosis-related genes were determined in vitro. Additionally, pathological scores, collagen volume fraction ( CVF) as well as levels of inflammation- and hepatic injury-associated genes were determined in in vivo. Down-regulated miR-150-5p and elevated CXCL1 expression levels were detected in HF tissues. ADMSCs-derived EVs transferred miR-150-5p to HSCs. CXCL1 was further verified as the downstream target gene of miR-150-5p. Moreover, ADMSCs-EVs containing miR-150-5p markedly inhibited HSC proliferation and activation in vitro. Meanwhile, in vivo experiments also concurred with the aforementioned results as demonstrated by inhibited CVF, reduced inflammatory factor levels and hepatic injury-associated indicators. Both experiments results were could be reversed by CXCL1 over-expression. Collectively, our findings indicate that ADMSCs-derived EVs containing miR-150-5p attenuate HF by inhibiting the CXCL1 expression. |
| Keywords: | adipose-derived mesenchymal stem cells extracellular vesicles hepatic fibrosis hepatic stellate cells MicroRNA-150-5p |