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MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6Clo Phenotype
- Source :
- Frontiers in Immunology, Vol 12 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- Emerging evidences have highlighted the crucial role of microRNAs (miRNAs) in the liver cirrhosis, but the relationship between miR-130a-3p and liver cirrhosis is not entirely clear. As we all know, schistosomiasis, as one of the zoonoses, can lead to liver cirrhosis when it advances. In this study, we investigated the biological functions of miR-130a-3p on the liver fibrosis of schistosomiasisin vivoandin vitro. The mice infected withSchistosoma japonicum(S. japonicum)were treated with lentivirus vector (LV)-miR-130a-3p by hydrodynamic injection through the tail vein. Our findings showed significantly decreased expression of miR-130a-3p both in the serum of patients with cirrhosis and in the liver of mice infected withS. japonicum. The results showed that LV-miR-130a-3p could effectively enter into the liver and alleviate liver granulomatous inflammation and collagen deposition. Simultaneously, LV-miR-130a-3p-promoted macrophages presented the Ly6Clophenotype, concomitant with the decreased expression of the tissue inhibitor of metalloproteinases (TIMP) 1, and increased the expression of matrix metalloproteinase (MMP) 2, which contributed to the dissolution of collagen. Furthermore, overexpression of miR-130a-3p not only inhibited the activation and proliferation of hepatic stellate cells (HSCs) but also induced the apoptosis of HSCs. In addition, we also confirmed that miR-130a-3p enables to bind with mitogen-activated protein kinase (MAPK) 1 and transforming growth factor-beta receptors (TGFBR) 1 and TGFBR2 genes and inhibit the expressions of these genes. Our findings suggested that miR-130a-3p might represent as the potential candidate biomarker and therapeutic target for the prognosis identification and treatment of schistosomiasis liver fibrosis.
- Subjects :
- 0301 basic medicine
Cirrhosis
Immunology
miR-130a-3p
Schistosomiasis
Biology
Matrix metalloproteinase
Ly6Clo
03 medical and health sciences
0302 clinical medicine
schistosomiasis
HSCs
medicine
Macrophage
Immunology and Allergy
Receptor
liver fibrosis
Schistosoma japonicum
RC581-607
medicine.disease
biology.organism_classification
030104 developmental biology
Apoptosis
030220 oncology & carcinogenesis
Cancer research
Hepatic stellate cell
Immunologic diseases. Allergy
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....2d29ffcbc4cd4373c6ce90b392f831e6
- Full Text :
- https://doi.org/10.3389/fimmu.2021.696069