Hepatosit Büyüme Faktörü (Hgf) ile Lisanslanmış Mezenkimal Kök Hücrelerde Anti-Fibrotik mİRNA İfade Düzeyleri

Abstract

Alişan, AB., Expression Levels Of Anti-Fibrotic miRNA's in Hepatocyte Growth Factor (HGF) Primed Mesenchymal Stem Cells, Hacettepe University Graduate School of Health Sciences Stem Cell Program Master’s Thesis, Ankara, 2024. Mesenchymal stem cells (MSCs) play a critical role in wound healing and fibrosis formation. The cytokines, chemokines and growth factors they secrete are directly involved in the physiopathogenesis of fibrosis and the actual healing of tissue damage. In vivo and in vitro studies on Hepatocyte Growth Factor (HGF), one of the growth factors secreted by MSCs, have shown that MSCs stimulated with HGF are more resistant to hypoxia and apoptosis, their proliferation and migration potential is increased, and their tissue repair capacity is enhanced by its immunoregulatory effect. Antifibrotic miRNAs are also secreted into the environment and they inhibit the mechanisms necessary for the progression of fibrosis by degrading the gene transcripts they target. In this study, we quantified the antifibrotic miRNAs whose expression changed in cells after priming human bone marrow-derived MSCs (BM-MSC) with HGF, and three miRNAs whose expression level changed more than two-fold with HGF priming were identified. Among these, miR-32-5p (fibrotic) and miR-377-3p (anti-fibrotic) expression have been increased and miR-10a-5p (fibrotic) expression has been decreased. As a result of searching the targets of these miRNAs in databases, when the common targets of the three miRNAs were evaluated focused on TGF-β, WNT and Hippo pathways, which are among the main mechanisms of fibrosis, indicated that HGF priming provided antifibrotic properties to the MSCs. It was also shown that HGF does not affect viability, accelerates wound healing and restricts population doubling. When we examined the effects of licensing by coculturing HGF-MSCs with a transwell system on the fibrosis model in which we induced myofibroblast differentiation by TGF-β induction, we could not detect a fibrosis-resolving effect. In order to demonstrate the biological significance of our findings, the results need to be evaluated with more detailed characterizations.