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

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 (Hgcl 2 )-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.

Exosomal‑miR‑1184 derived from mesenchymal stem cells alleviates cisplatin‑associated acute kidney injury

“…MicroRNAs (miRNAs/miRs) are a novel class of non-coding small ribonucleic acids, which can regulate gene expression by suppression of mRNA translation or degradation of mRNAs ( 11 , 12 ). Moreover, miRNAs participate in cellular process, including the growth of renal tubular epithelial cells ( 13 , 14 ). Meanwhile, miRNAs have been reported to be associated with AKI progression ( 15 – 17 ).…”

Plasma Exosomal Non-Coding RNA Profile Associated with Renal Damage Reveals Potential Therapeutic Targets in Lupus Nephritis

“…A previous study has shown that up-regulation of miR-101 inhibits acute kidney injury and chronic kidney disease transition by regulating epithelial–mesenchymal transition [ 21 ]. Another work demonstrated that miR-101-3p is a regulator of renal interstitial fibrosis inhibiting TGF-β1-induced tubular EMT by targeting TβR-I [ 22 ]. Zhao et al revealed that miR-101-3p negatively regulates inflammation in SLE via MAPK1 targeting and blocking the NF-κB pathway [ 23 ].…”

Association between Circulating MicroRNAs (miR-21-5p, miR-20a-5p, miR-29b-3p, miR-126-3p and miR-101-3p) and Chronic Allograft Dysfunction in Renal Transplant Recipients

“…miR-101-3p has been reported on over the last 3 years. Wang et al found miR-101 reverse TGFβ1 induced epithelial-to-mesenchymal transition (EMT) in HK 2 cells with less fibrosis [ 33 ]. Zhao et al also revealed that miR-101 inhibits AKI-to-CKD transition by regulating EMT [ 34 ].…”