Bone marrow MSCs-derived exosomes (BM-MSCs-Exo) expressed mir-181, mir-24, mir-9, mir-29, mir-338, and mir-486 ameliorated hepatic fibrosis in male rats via altering the expression of Menin-1/TGF-β/Smad pathway.

Abstract

Bone marrow mesenchymal stem cells derived exosomes (BM-MSC-Exo) expressed a variety of microRNAs in their secretome however their role in alleviating hepatic fibrosis remains elusive. Thus, the present study was designed to investigate the role of the miRNAs conveyed by BM-MSC-Exo in reversing hepatic fibrosis in male rats. Seventy-five adult male Sprague Dawley rats were allocated into 5 equal groups 15 rats each, control, fibrosis, fibrosis + conditioned media (CM), fibrosis + EX, and fibrosis + BM-MSCs. The expression levels of mir-181a-2-3p, mir-24, mir-181a-5p, mir-9a-5p, mir-29a, mir-338-5p, and mir-486 in BM-MSCs, EX, CM, and hepatic tissue of the experimental animals were analyzed. Moreover, their impact on modulating hepatic: Menin-1 - TGF-β/ Smad fibrotic signaling pathway, inflammation, apoptosis, and angiogenesis was investigated. The results revealed a significant upregulation in the expression of mir-181a-2-3p, mir-24, mir-181a-5p, mir-9a-5p, mir-29a, mir-338-5p, and mir-486 in BM-MSCs-Exo and its treated rats' group than BM-MSCs, CM, and their rat treated groups. Moreover, there were significant improvements in hepatic: Menin-1 - TGF-β/ Smad fibrotic signaling pathway oxidative stress, apoptosis, and angiogenesis in the Exo-treated group than the other experimental group. It could be concluded that BM-MSCs-Exo alleviates hepatic fibrosis more than BM-MSCs by conveying a higher cargo of miRNAs.