Affiliation:
1. The 2nd Affiliated Hospital of Harbin Medical University: Second Affiliated Hospital of Harbin Medical University
2. Harbin Medical University
3. Second Affiliated Hospital of Harbin Medical University
Abstract
Abstract
Background: Liver fibrosis (LF) is the pathological basis of a majority of chronic liver diseases, characterized by excessive activation of hepatic stellate cells (HSCs), inflammatory disorders and progressive scarring of the hepatic interstitial. Recently, sing-cell RNA sequencing (scRNA-seq) technology highlighted a much greater diversity between quiescent HSCs (qHSCs) and activated HSCs (aHSCs) in the progression of LF. Our study aims to investigate the role of Eif5a in liver fibrosis.
Methods: Bioinformatic analysis showed that the expression of Eif5a was associated with aHSCs. Immunofluorescence staining and qRT-PCR assays were performed to detected the expression and localization of Eif5a in both in vitro and in vivo hepatic fibrosis models. CCK-8, EdU, wound healing and flow cytometry assays verified the effect of si-EIF5A on aHSCs. H&E staining, Masson staining and immunohistochemistry assays detected the function of AAV-sh-Eif5a on mouse liver fibrosis. Further, transmission electron microscopy, mitochondrial membrane potential, Mito-Tracker Green, OCR and ATP experiments confirmed the relationship between EIF5A and mitochondrial biogenesis.
Results: Functionally, the silencing of Eif5a inhibited proliferation, migration, differentiation, and extracellular matrix deposition in aHSCs from both human and mouse origin. In vivo experiments, we found that silencing Eif5a slightly alleviated CCL4-induced liver fibrosis. Mechanistically, mitigating EIF5A triggered the mitochondrial morphology and function disorders to alleviated aHSCs activation.
Conclusions: In summary, our findings reveal that inhibition of EIF5A can alleviate LF through inhibiting mitochondrial function.
Publisher
Research Square Platform LLC
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