Iranian Biomedical Journal

en Unraveling the Exosome-miR-133a Axis: Targeting TGF-β Signaling via WJ-MSC-Derived Exosomes for Anti-Fibrotic Therapy in Liver Fibrosis Molecular Genetics & Genomics Molecular Genetics & Genomics مقاله کامل Full Length/Original Article <div style="text-align: justify;">Background: One of the primary drivers of liver fibrosis is the excessive accumulation of extracellular matrix (ECM), primarily caused by the over-proliferation of hepatic star-shaped cells (HSCs). The activation of HSCs by transforming growth factor beta (TGF-β) has a critical role in initiating fibrosis. Recent studies have suggested that miRNA-133a significantly regulates the fibrogenesis process, which its downregulation is associated with the fibrosis progression. Understanding the role of miRNA-133a provides potential therapeutic insights for targeting TGF-β signaling and mitigating liver fibrosis. We investigated whether exosomes could attenuate liver fibrosis by enhancing the antifibrotic effects of miR-133a. Methods: The LX-2 cell line was treated with TGF-β for 24 hours, followed by an additional 24 hours of treatment with exosomes. After this treatment period, we assessed the mRNA expression levels of α-SMA, collagen 1, and miR-133a, as well as the protein levels of p-Smad3. Results: TGF-β exposure significantly increased the expression level of α-SMA and collagen 1 genes and elevated the levels of p-Smad3 protein. Additionally, it resulted in a significant downregulation of miR-133a compared to the control group. Exosome administration effectively reduced the TGF-β-induced upregulation of p-Smad3, α-SMA, and collagen 1 genes, but increased miR-133a expression levels. Conclusion: Our findings indicate that by partially mitigating the downregulation of miR-133a, exosomes can effectively inhibit the persistent activation of HSCs. Furthermore, in the context of in vitro liver fibrosis, exosomes can suppress the TGF-β/Smad3 pathway, reducing the accumulation of ECM.  </div> Exosomes, Hepatic stellate cells, Liver fibrosis, MicroRNAs 235 244 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-5980-1&slc_lang=en&sid=1 Sahar Saki saharsaki23@gmail.com 0009-0006-7525-6627 No Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Sajad Monjezi sajadmonjexii@gmail.com 0009-0005-0044-7464 No Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Fatemeh Ghaffari fatimaghf34@gmail.com 0009-0003-1027-0493 No Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Ghazal Orak ghazaljon67@gmail.com 0000-0002-0054-2702 No Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Samaneh Salehipour Bavarsad samanehS.B64@gmail.com 0000-0001-7336-2166 No Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Azam Khedri azamkhedri56@gmail.com 0000-0001-9623-1054 No Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Mahdi Hatami mahdihatami6268@gmail.com 0000-0002-7810-5780 Yes Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran