Li Huicong, Wang Yunqian, Chen Baoping, Shi Jun
Department of Nephrology, Huaihe Hospital of Henan University No. 115 Ximen Street Kaifeng 475000 Henan Province China
RSC Adv. 2019 Feb 28;9(12):6928-6934. doi: 10.1039/c8ra10369k. eCollection 2019 Feb 22.
Transmembrane protein 88 (TMEM88) belongs to a member of the TMEM family, and was reported to be involved in fibrogenesis. However, the biological role of TMEM88 in renal fibrosis has not been elucidated. Therefore, the objective of this study was to investigate the effect of TMEM88 on cell proliferation and extracellular matrix (ECM) accumulation in a TGF-β1-induced human renal proximal tubular epithelial cell line (HK2). Our results showed that TMEM88 was downregulated in renal fibrotic tissues and TGF-β1-treated HK2 cells. In addition, TMEM88 overexpression inhibited TGF-β1-induced cell proliferation and migration in HK2 cells. Furthermore, TMEM88 overexpression reduced the production of α-SMA, collagen I, and collagen III in TGF-β1-stimulated HK2 cells. Mechanistically, TMEM88 overexpression suppressed the phosphorylation status of Smad2 and Smad3 in TGF-β1-stimulated HK2 cells. In conclusion, data from our experiments demonstrate that TMEM88 plays a pivotal role in the pathological process of renal fibrosis. TMEM88 inhibited fibrosis in renal proximal tubular epithelial cells by suppressing the TGF-β1/Smad signaling pathway.
跨膜蛋白88（TMEM88）属于跨膜蛋白家族成员，据报道其参与了纤维化形成过程。然而，TMEM88在肾纤维化中的生物学作用尚未阐明。因此，本研究的目的是探讨TMEM88对转化生长因子-β1（TGF-β1）诱导的人肾近端小管上皮细胞系（HK2）细胞增殖和细胞外基质（ECM）积聚的影响。我们的结果显示，TMEM88在肾纤维化组织和TGF-β1处理的HK2细胞中表达下调。此外，TMEM88过表达抑制了TGF-β1诱导的HK2细胞增殖和迁移。而且，TMEM88过表达减少了TGF-β1刺激的HK2细胞中α-平滑肌肌动蛋白（α-SMA）、I型胶原和III型胶原的产生。机制上，TMEM过表达抑制了TGF-β1刺激的HK2细胞中Smad2和Smad3的磷酸化状态。总之，我们实验的数据表明TMEM88在肾纤维化的病理过程中起关键作用。TMEM88通过抑制TGF-β1/Smad信号通路抑制肾近端小管上皮细胞纤维化。
