Abstract

Pleural fibrosis is an irreversible pathological process occurred in the development of several lung diseases. TMEM88 is a member of transmembrane (TMEM) family and has been found to be involved in the regulation of fibrogenesis. However, the role of TMEM88 in pleural fibrosis remains unknown. In this study, we aimed to explore the role of TMEM88 in pleural fibrosis in vitro using transforming growth factor-β1 (TGF-β1)-induced human pleural mesothelial cell line MeT-5A cells. Our results showed that the expression levels of TMEM88 were downregulated in pleural fibrosis tissues and TGF-β1-treated Met-5A cells. Overexpression of TMEM88 inhibited the proliferation of Met-5A cells under TGF-β1 stimulation. In addition, TMEM88 overexpression prevented TGF-β1-induced extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) in Met-5A cells with decreased expression levels of Col I and fibronectin, increased levels of cytokeratin-8 and E-cadherin, as well as decreased levels of vimentin and α-SMA. Furthermore, overexpression of TMEM88 inhibited the expression of TGF-β receptor I (TβRI) and TβRII and suppressed the phosphorylation of Smad2 and Smad3 in Met-5A cells. In conclusion, these results indicated that TMEM88 exhibited an anti-fibrotic activity in pleural fibrosis via inhibiting the activation of TGF-β1/Smad signaling pathway.

摘要

胸膜纤维化是一种不可逆的病理过程，发生在多种肺部疾病的发展过程中。TMEM88 是跨膜 (TMEM) 家族的成员，已被发现参与纤维发生的调节。然而，TMEM88 在胸膜纤维化中的作用仍然未知。在本研究中，我们旨在探索 TMEM88在体外在胸膜纤维化中的作用使用转化生长因子-β1 (TGF-β1) 诱导的人胸膜间皮细胞系 MeT-5A 细胞。我们的结果表明，TMEM88 的表达水平在胸膜纤维化组织和 TGF-β1 处理的 Met-5A 细胞中下调。TMEM88的过表达抑制了TGF-β1刺激下Met-5A细胞的增殖。此外，TMEM88 过表达可防止 Met-5A 细胞中 TGF-β1 诱导的细胞外基质 (ECM) 积累和上皮间质转化 (EMT)，降低 Col I 和纤连蛋白的表达水平，增加细胞角蛋白-8 和 E-钙粘蛋白的水平，以及波形蛋白和α-SMA的水平降低。此外，TMEM88 的过表达抑制了 TGF-β 受体 I (TβRI) 和 TβRII 的表达，并抑制了 Met-5A 细胞中 Smad2 和 Smad3 的磷酸化。综上所述，通过抑制 TGF-β1/Smad 信号通路的激活。