MicroRNA-101 suppresses liver fibrosis by downregulating PI3K/Akt/mTOR signaling pathway - 29/09/19
pages | 10 |
Iconographies | 4 |
Vidéos | 0 |
Autres | 0 |
Highlights |
• | MiR-101 has antifibrotic effect in experimental liver fibrosis. |
• | Down-regulating PI3K/Akt/mTOR signaling pathway is involved in the antifibrotic mechanisms of miR-101. |
• | The roles of miR-101 in liver fibrosis suggest that it could be a potential therapeutic target for liver fibrosis. |
Summary |
Background |
MicroRNA-101 (miR-101) is markedly downregulated in both hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma (HCC). In this study, we aimed to investigate the effect and mechanism of miR-101 on hepatic stellate cell (HSC) activation and liver fibrosis.
Materials and methods |
HSC LX-2 was treated with TGF-β1 and with or without miR-101 mimics. LX-2 vitality and proliferation, the expression of F-actin and mRNAs for α-SMA, collagen 1α1 (Col 1α1), and connective tissue growth factor 2 (CCN2) were measured. A 6-week intraperitoneal injection of carbon tetrachloride (CCl4) was used to induce experimental liver fibrosis in mice, which were treated using a miR-101 negative control or miR-101 agomir from the fourth week until the end of the experiment. Liver function, hepatic hydroxyproline, liver histopathology, collagen deposition, α-SMA, type I collagen (Col I) and the protein-expressions of p-PI3K, p-Akt and p-mTOR were measured.
Results |
MiR-101 significantly suppressed the increased LX-2 vitality and high accumulation of extracellular matrix (ECM) induced by TGF-β1. Exposure to CCl4 led to the impairment of liver function and disruption of normal hepatic parenchyma in mice, as well as obvious liver fibrosis indicated by elevated levels of hydroxyproline, α-SMA, and Col 1α1 in liver tissues. MiR-101 administration significantly improved liver function, relieved hepatic parenchyma damage, and reversed liver fibrosis by decreasing the accumulation of ECM components. Furthermore, miR-101 substantially downregulated the CCl4-increased p-PI3K, p-Akt, and p-mTOR in mouse liver.
Conclusions |
MiR-101 has antifibrotic effects in experimental liver fibrosis, and downregulating the PI3K/Akt/mTOR signaling pathway may be one of its antifibrotic mechanisms.
Le texte complet de cet article est disponible en PDF.Abbreviations : miR-101, HCC, HSC, CCN2, mTOR, Col I, PI3K, Akt
Keywords : Microrna-101, Liver fibrosis, PI3K/Akt/mTOR signaling pathway
Plan
Vol 43 - N° 5
P. 575-584 - octobre 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.
Déjà abonné à cette revue ?