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.

中文翻译：

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MicroRNA-708通过直接靶向TMEM88调节肝星状细胞的活化并增强细胞外基质的积累。

跨膜蛋白88（TMEM88）是一种潜在的2跨膜型蛋白，可与Dishevelled-1（DVL-1）的PDZ结构域相互作用，Dishevelled-1（DVL-1）是Wnt信号通路通过其C端Val-Trp-Val（VWV）的重要组成部分）在非洲爪蟾胚胎细胞中的基序。由于β-catenin在肝纤维化中的重要作用，因此迫切需要研究TMEM88在肝纤维化中的作用机制。目前的研究是为了评估TMEM88在肝纤维化过程中的功能并阐明其内在机制。研究发现，TMEM88在人纤维化肝组织中减少。在功能上，TMEM88显着降低了α-平滑肌肌动蛋白（α-SMA）和I型胶原的表达水平（Col. I）和通过恢复基质金属蛋白酶（MMP）和TIMP（金属蛋白酶的组织抑制剂）之间的平衡来抑制细胞外基质（ECM）的积累。TMEM88通过调节Wnt /β-catenin信号通路的Wnt3a，Wnt2b和β-catenin抑制HSCs增殖并评估活化LX-2细胞的凋亡。此外，我们证明了miR-708特别针对TMEM88 3'-UTR区，并下调了TGF-β1刺激的LX-2细胞中TMEM88的表达水平。MiR-708促进了激活的LX-2细胞中ECM的生成和细胞活化。这些结果表明，miR-708可以通过Wnt /β-catenin信号通路直接靶向TMEM88来促进HSC活化并增强ECM积累。这将为将来肝纤维化过程的研究提供潜在的目标。