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Mesenchymal stem cells (MSCs) and human umbilical cord MSC-derived exosomes (hUC-MSCs-Exos) based therapy has been widely regarded as a potential strategy for the treatment of hepatic fibrosis, and the aim of the present study was to investigate the effects of human umbilical cord MSCs (hUC-MSCs) and hUC-MSCs-Exos on hepatic fibrosis and to reveal their potential mechanisms of action. By constructing an animal model of carbon tetrachloride (CCl4)-induced hepatic fibrosis, observing the histomorphological and pathological changes, and combining the changes in liver function indices, inflammatory factor levels and peroxide content, we comprehensively evaluated the anti-fibrotic ability of hUC-MSCs and hUC-MSCs-Exos. Meanwhile, miRNA sequencing (miRNA-seq) technology was used to screen for the differentially expressed genes, and the role of hUC-MSCs and hUC-MSCs-Exos on the regulation of proteins related to the Wnt/β-catenin signaling pathway was verified with the help of protein immunoblotting (Western blot, WB). All protocols and procedures were approved by the Animal Ethics Committee of the Animal Experiment Center of Xinjiang Medical University, and all experimental procedures complied with Chinese regulations concerning laboratory animals (approval No.: IACUC-JT-20240627-26). The results showed that both hUC-MSCs and hUC-MSCs-Exos could effectively alleviate hepatic fibrosis by reducing collagen accumulation, improving liver function, inhibiting inflammation, and decreasing oxidative stress, and hUC-MSCs-Exos was more effective than hUC-MSCs in treating hepatic fibrosis; at the same time, both of them could down-regulate the expression of Wnt/β-catenin pathway components (Wnt3a, β-catenin, WISP1/CCN4, cyclin D1) in the hepatic fibrosis tissues. In addition, miRNA-seq results further indicated that the expression of miRNA-184 was significantly involved in the regulation of this pathway. The findings in this paper confirmed that both hUC-MSCs and hUC-MSCs-Exos improved liver fibrosis in rats, and the antifibrotic effect of hUC-MSCs-Exos may be related to the Wnt/β-catenin signaling pathway, which provides an effective therapeutic strategy for the treatment of liver fibrosis.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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