Affiliation: | 1. Department of Imaging, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China Xin Liao and Wei Zhan contributed equally to the work.;2. Surgery of Colorectal, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China Xin Liao and Wei Zhan contributed equally to the work.;3. Doctoral Graduate Student of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China;4. Department of Pathology, Guiyang Maternal and Child Health Hospital, Guiyang, Guizhou, China;5. Department of Traditional Chinese Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China;6. Department of Pathology and Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China |
Abstract: | Hepatic fibrosis is a chronic inflammatory and reversible repair reaction of the liver under the continuous action of virus or various injuries. In this study, we aimed at identifying the role of miR-326 in the hepatic stellate cell (HSC) activation and liver fibrosis and its potential mechanism. In this study, the liver fibrosis mouse model was developed by injecting CCl4. Liver tissue morphology was observed and the expression level of α-smooth muscle actin, collagen1α1 and miR-326 was measured. Target gene identification was performed by loss-of-function and gain-of-function. The effect of miR-326 on the expression level of the cytokines associated with the TLR4/MyD88/nuclear factor-κB (NF-κB) pathway was assessed in vitro and in vivo. We show that miR-326 was downregulated in CCl4-induced fibrotic mice and activated HSCs. The target gene of miR-326 is TLR4. Moreover, miR-326 inhibited the activation of HSCs in vitro through TLR4/MyD88/NF-κB signaling. miR-326 attenuated hepatic fibrosis and inflammation of CCl4-induced mice in vivo. Our results demonstrate for the first time that miR-326 inhibits HSC activation through TLR4/MyD88/NF-κB signaling. Furthermore, miR-326 plays critical roles in attenuating liver fibrosis and inflammation, suggesting the therapeutic potential of miRNAs. |