Iranian
Biomedical Journal
Volume 28, Issue 5 And 6 (9-2024)
IBJ 2024, 28(5 And 6): 235-244 |
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Ethics code: IR.AJUMS.REC.1400.461
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Saki S, Monjezi S, Ghaffari F, Orak G, Salehipour Bavarsad S, Khedri A et al . Unraveling the Exosome-miR-133a Axis: Targeting TGF-β Signaling via WJ-MSC-Derived Exosomes for Anti-Fibrotic Therapy in Liver Fibrosis. IBJ 2024; 28 (5 and 6) :235-244
URL: http://ibj.pasteur.ac.ir/article-1-4357-en.html
URL: http://ibj.pasteur.ac.ir/article-1-4357-en.html
Sahar Saki 
, Sajad Monjezi , Fatemeh Ghaffari , Ghazal Orak , Samaneh Salehipour Bavarsad , Azam Khedri , Mahdi Hatami *
, Sajad Monjezi , Fatemeh Ghaffari , Ghazal Orak , Samaneh Salehipour Bavarsad , Azam Khedri , Mahdi Hatami *
Abstract:
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.
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.
Type of Study: Full Length/Original Article |
Subject:
Molecular Genetics & Genomics
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