MicroRNA-708 modulates Hepatic Stellate Cells activation and enhances extracellular matrix accumulation via direct targeting TMEM88
| Autor: | Haodong Li, Chen-chen Yang, Li Liangyun, Jun Li, Xiao-Ming Meng, Shuang Hu, Tao Xu, Yuming Liu, Hong Zhou, Lin-xin Pan, Junfa Yang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis Male Apoptosis Matrix metalloproteinase Cell Line Extracellular matrix Transforming Growth Factor beta1 03 medical and health sciences 0302 clinical medicine microRNA Hepatic Stellate Cells Humans LX‐2 cells Wnt Signaling Pathway Cell Proliferation liver fibrosis miR‐708 TMEM88 Chemistry Wnt signaling pathway Membrane Proteins Tissue Inhibitor of Metalloproteinases Cell Biology Original Articles Middle Aged Hedgehog signaling pathway Matrix Metalloproteinases Cell biology Extracellular Matrix MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Hepatic stellate cell Molecular Medicine Female Original Article Cell activation WNT3A |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 |
| Popis: | Transmembrane protein 88 (TMEM88) is a potential 2‐transmembrane‐type protein that interacts with the PDZ domain of Dishevelled‐1 (DVL‐1), a crucial component of Wnt signalling pathway through its C‐terminal Val‐Trp‐Val (VWV) motif in Xenopus embryo cells. Since the significant function of β‐catenin in liver fibrosis, it is urgent to study the TMEM88 mechanism in liver fibrosis. The current research was for evaluating the function of TMEM88 in the process of the liver fibrosis and clarifying the inherent mechanism. The study found that TMEM88 is decreased in human fibrotic liver tissues. Functionally, TMEM88 significantly reduced the expression levels of α‐smooth muscle actin (α‐SMA) and collagen type I (Col.I) and repressed extracellular matrix (ECM) accumulation by restoring the balance between matrix metalloproteinases (MMPs) and TIMPs (tissue inhibitor of metalloproteinases). TMEM88 inhibited HSCs proliferation and evaluated the apoptosis of activated LX‐2 cells by regulating Wnt3a, Wnt2b and β‐catenin of Wnt/β‐catenin signalling pathway. Moreover, we demonstrated that miR‐708 particularly targeted TMEM88 3′‐UTR regions and down‐regulated the expression level of TMEM88 in TGF‐β1‐stimulated LX‐2 cells. MiR‐708 promoted the generation of ECM and cell activation in activated LX‐2 cells. These results determined that miR‐708 could promote HSCs activation and enhance ECM accumulation via direct targeting TMEM88 by Wnt/β‐catenin signalling pathway. This will provide a potential target for future research in the process of liver fibrosis. |
| Databáze: | OpenAIRE |
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