Serum-derived miR-574-5p-containing exosomes contribute to liver fibrosis by activating hepatic stellate cells

• Published in: Molecular biology reports 2022-03, Vol.49 (3), p.1945-1954
• Main Authors: Zhou, Xia, Liang, Ziyu, Qin, Shanyu, Ruan, Xianxian, Jiang, Haixing
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Animals; Biomedical and Life Sciences; Carbon tetrachloride; Cell Line; Cell Proliferation; Centrifugation; Cirrhosis; Collagen; Collagen (type I); Confocal microscopy; Exosomes; Exosomes - metabolism; Fibrosis; Hepatic Stellate Cells - metabolism; Histology; Humans; Life Sciences; Liver; Liver cirrhosis; Liver Cirrhosis - pathology; Mice; MicroRNAs - metabolism; Morphology; mRNA; Original; Original Article; Stellate cells
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-021-07008-2

Aim To investigate the association of serum exosomes miR-574-5p with liver fibrosis, and explore the effect and mechanism of serum exosomes on HSC activation. Materials and methods Using serum samples collected from healthy adults and patients with liver cirrhosis, we extracted human serum exosomes via ultra-high-speed centrifugation, and co-cultured them with hepatic stellate cells (HSCs) line LX2. LX-2-mediated intake of human serum exosomes was examined by confocal microscopy. To induce liver fibrosis, we administered 20% CCl 4 to mice intraperitoneally and adopted an exoEasy MIDI kit to extract serum exosomes.Liver fibrosis-related molecules were determined via qRT-PCR, Western blot, Masson staining, and Immunohistochemical staining. Results Significantly high miR-574-5p levels were expressed in serum exosomes and were positively correlated with the expression of miR-574-5p, collagen deposition, and α-SMA expression in liver tissues of mice during liver fibrosis. Compared to healthy subjects, serum exosomes from cirrhosis patients were associated with higher expression of miR-574-5p. MiR-574-5p mimic promoted the expression of α-SMA and COL1A1 mRNA and protein in LX-2, whereas miR-574-5p inhibitor exerted no effect. Conclusion This article demonstrates that miR-574-5p expression in serum exosomes is positively correlated with collagen deposition and HSC activation in liver tissues during liver fibrosis.Serum exosomes potentially activate HSC through the transfer of miR-574-5p to HSC during liver fibrosis.