MicroRNA‑101 inhibits renal tubular epithelial‑to‑mesenchymal transition by targeting TGF‑β1 type I receptor

Wang,Qinglan; Tao,Yanyan; Xie,Hongdong; Liu,Chenghai; Liu,Ping

doi:10.3892/ijmm.2021.4952

MicroRNA‑101 inhibits renal tubular epithelial‑to‑mesenchymal transition by targeting TGF‑β1 type I receptor

Authors:
- Qinglan Wang
- Yanyan Tao
- Hongdong Xie
- Chenghai Liu
- Ping Liu
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Affiliations: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: April 29, 2021 https://doi.org/10.3892/ijmm.2021.4952
Article Number: 119
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs/miRs) are key regulators of renal interstitial fibrosis (RIF). The present study was designed to identify miRNAs associated with the development of RIF, and to explore the ability of these identified miRNAs to modulate the renal tubular epithelial‑to‑mesenchymal transition (EMT) process. To this end, miRNAs that were differentially expressed between normal and fibrotic kidneys in a rat model of mercury chloride (HgCl₂)‑induced RIF were detected via an array‑based approach. Bioinformatics analyses revealed that miR‑101 was the miRNA that was most significantly downregulated in the fibrotic renal tissue samples, and this was confirmed by RT‑qPCR, which also demonstrated that this miRNA was downregulated in transforming growth factor (TGF)‑β1‑treated human proximal tubular epithelial (HK‑2) cells. When miR‑101 was overexpressed, this was sufficient to reverse TGF‑β1‑induced EMT in HK‑2 cells, leading to the upregulation of the epithelial marker, E‑cadherin, and the downregulation of the mesenchymal marker, α‑smooth muscle actin. By contrast, the downregulation of miR‑101 using an inhibitor exerted the opposite effect. The overexpression of miR‑101 also suppressed the expression of the miR‑101 target gene, TGF‑β1 type I receptor (TβR‑I), and thereby impaired TGF‑β1/Smad3 signaling, while the opposite was observed upon miR‑101 inhibition. To further confirm the ability of miR‑101 to modulate EMT, the HK‑2 cells were treated with the TβR‑I inhibitor, SB‑431542, which significantly suppressed TGF‑β1‑induced EMT in these cells. Notably, miR‑101 inhibition exerted a less pronounced effect upon EMT‑related phenotypes in these TβR‑I inhibitor‑treated HK‑2 cells, supporting a model wherein miR‑101 inhibits TGF‑β1‑induced EMT by suppressing TβR‑I expression. On the whole, the present study demonstrates that miR‑101 is capable of inhibiting TGF‑β1‑induced tubular EMT by targeting TβR‑I, suggesting that it may be an important regulator of RIF.

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