TGF-β regulates TGFBIp expression in corneal fibroblasts via miR-21, miR-181a, and Smad signaling
TGF-β regulates TGFBIp expression in corneal fibroblasts via miR-21, miR-181a, and Smad signaling
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DOI：
10.1016/j.bbrc.2016.02.086
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发表时间：
2016-03-25
影响因子：
3.1
通讯作者：
Kim, Eung Kweon
中科院分区：
文献类型：
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作者：
Choi, Seung-il;Jin, Jun-Yup;Kim, Eung Kweon
转化生长因子-β (TGF-β) 诱导基因 (TGFBI) 蛋白 (TGFBIp) 与 2 型颗粒性角膜营养不良 (GCD2) 相关。 TGFBIp水平可以影响GCD2表型，但潜在的分子机制尚未完全阐明。我们研究了 microRNA (miRNA) 和 TGF-β 在角膜成纤维细胞中 TGFBIp 表达调节中的作用。 miR-9、miR-21 和 miR-181a 的异位表达显着降低了 TGFBIp 水平。相反，TGF-β1诱导miR-21和miR-181a的表达。在角膜成纤维细胞中，miR-21的表达比miR-9和miR-181a高10倍。此外，角膜成纤维细胞中TGF-β1的表达显着高于TGF-β2和TGF-β3，而所有三种TGF-β形式的表达在野生型（WT）和GCD2纯合子（HO）角膜成纤维细胞之间没有显着差异。总之，这些数据表明TGFBIp表达受TGF-β正向调节，而TGF-β诱导的miR-21和miR-181a负向调节TGFBIp表达。总之，角膜成纤维细胞中的 TGFBIp 水平是通过 miR-21 和 miR-181a 的协调活性以及 Smad 信号传导来控制的。这些 miRNA 和 TGF-β 信号传导的药理学调节可能对 TGFBI 相关的角膜营养不良（包括 GCD2）具有治疗潜力。 (C) 2016 Elsevier Inc. 保留所有权利。
Transforming growth factor-beta (TGF-beta)-induced gene (TGFBI) protein (TGFBIp) is associated with granular corneal dystrophy type 2 (GCD2). TGFBIp levels can affect GCD2 phenotypes, but the underlying molecular mechanisms have not been fully elucidated. We investigated the involvement of microRNA (miRNA) and TGF-beta in the regulation of TGFBIp expression in corneal fibroblasts. Ectopic expression of miR-9, miR-21, and miR-181a significantly decreased TGFBIp levels. Conversely, expression of miR-21 and miR-181a was induced by TGF-beta 1. Expression of miR-21 was 10-fold higher than that of miR-9 and miR-181 a in corneal fibroblasts. Additionally, TGF-beta 1 expression was significantly higher than that of TGF-beta 2 and TGF-beta 3 in corneal fibroblasts, whereas expression of all three TGF-beta forms was not significantly different between wild-type (WT) and GCD2 homozygotes (HO) corneal fibroblasts. Taken together, these data indicate that TGFBIp expression is positively regulated by TGF-beta, whereas TGF-beta-induced miR-21 and miR-181a negatively regulate TGFBIp expression. In conclusion, TGFBIp levels in corneal fibroblasts are controlled via the coordinated activity of miR-21 and miR-181a and by Smad signaling. Pharmacologic modulation of these miRNAs and TGF-beta signaling could have therapeutic potential for TGFBI-associated corneal dystrophy, including GCD2. (C) 2016 Elsevier Inc. All rights reserved.