MicroRNA-21a-5p regulates TGF-?1-induced myofibroblast transformation of rabbit keratocytes by targeting Smad7

IF 1 4区 综合性期刊 Q3 MULTIDISCIPLINARY SCIENCES
Jianhai Bai, Minli Zhang, Xiaomin Ding, Xingzhi Yang, Daniel Zheng, Hongyun Mou, Xiaoxiao Ruan, Yueqing Feng, Hai-xiong Han, Shi-li Wang
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引用次数: 1

Abstract

The transforming growth factor β1 (TGF-β1)-induced transformation of keratocytes to myofibroblasts is a very common process during corneal wound healing, but a dysregulated TGF-β1 activity may induce unfavorable fibrosis and scar formation in the cornea. MicroRNA (miR)-21a-5p and Smad7 have been reported to play an important role in the fibrosis process. However, how miR-21a-5p involves in the TGF-β1-induced myofibroblasts transformation of keratocytes remains unclear. In the present study, we found an increase in the expressions of α-SMA and collagen I at protein level as well as Smad7 and miR-21a-5p at mRNA level when keratocytes were treated with TGF-β1Here; but the Smad7 at protein level kept unchanged. The overexpression of miR-21a-5p attenuated Smad7 protein expression, and miR-21a-5p inhibition promoted Smad7 protein expression without affecting its mRNA expression. Furthermore, inhibition of miR-21a-5p could decrease TGF-β1-inducedα-SMA expression, whereas the addition of Smad7 knockdown would rescue the expression of α-SMA. These results suggested that miR-21a-5p had a promoting effect on TGF-β1induced myofibroblast transformation of keratocytes by targeting Smad7 at its translation stage.
微小RNA-21a-5p调节TGF-?靶向Smad7诱导1诱导的兔角膜细胞肌成纤维细胞转化
转化生长因子β1 (TGF-β1)诱导角质细胞向肌成纤维细胞的转化是角膜创面愈合过程中非常常见的过程,但TGF-β1活性失调可能导致角膜不利的纤维化和瘢痕形成。据报道,MicroRNA (miR)-21a-5p和Smad7在纤维化过程中发挥重要作用。然而,miR-21a-5p如何参与TGF-β1诱导的角质细胞的肌成纤维细胞转化尚不清楚。在本研究中,我们发现TGF-β1处理角化细胞后,蛋白水平α-SMA和胶原I的表达增加,mRNA水平Smad7和miR-21a-5p的表达增加;而蛋白水平的Smad7则保持不变。过表达miR-21a-5p可减弱Smad7蛋白的表达,抑制miR-21a-5p可促进Smad7蛋白的表达,但不影响其mRNA的表达。此外,抑制miR-21a-5p可降低TGF-β1诱导的α-SMA表达,而添加Smad7敲低可挽救α-SMA的表达。这些结果表明,miR-21a-5p通过靶向翻译阶段的Smad7,对TGF-β1诱导的角化细胞的肌成纤维细胞转化具有促进作用。
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来源期刊
Scienceasia
Scienceasia MULTIDISCIPLINARY SCIENCES-
CiteScore
1.70
自引率
33.30%
发文量
102
审稿时长
1 months
期刊介绍: ScienceAsia is a multidisciplinary journal publishing papers of high quality bimonthly, in printed and electronic versions, by the Science Society of Thailand under Royal Patronage and the National Research Council of Thailand. The journal publishes original research papers that provide novel findings and important contribution to broad area in science and mathematics. Areas covered include Biological Sciences and Biotechnology, Chemistry and Material Sciences, Environmental and Applied Sciences, and Mathematics and Physical Sciences. Manuscripts may report scientifically useful data, observations or model predictions, and/or provide a new scientific concept or a new explanation of published results. Submissions of materials of current scientific interest are highly welcome, provided that there is sufficient scientific merit. The journal will not accept manuscripts which have been published or are being considered for publication elsewhere, nor should manuscripts being considered by ScienceAsia be submitted to other journals. Submitted manuscripts must conform to the guidelines given in the Instructions for Authors
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