MicroRNA‑181 exerts an inhibitory role during renal fibrosis by targeting early growth response factor‑1 and attenuating the expression of profibrotic markers

Zhang,Xiaoyan; Yang,Zhenning; Heng,Yanyan; Miao,Congxiu

doi:10.3892/mmr.2019.9964

MicroRNA‑181 exerts an inhibitory role during renal fibrosis by targeting early growth response factor‑1 and attenuating the expression of profibrotic markers

Authors:
- Xiaoyan Zhang
- Zhenning Yang
- Yanyan Heng
- Congxiu Miao
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Affiliations: Department of Nephrology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China, School of Clinical Medicine, Norman Bethune Health Science Center of Jilin University, Changchun, Jilin 130022, P.R. China, Department of Scientific Research, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China
Published online on: February 18, 2019 https://doi.org/10.3892/mmr.2019.9964
Pages: 3305-3313

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Abstract

Progressive renal fibrosis is a common complication of chronic kidney disease that results in end‑stage renal disorder. It is well established that several microRNAs (miRs) function as critical regulators implicated in fibrotic diseases. However, the role of miR‑181 in the development and progression of renal fibrosis remains unclear, and the precise mechanism has not yet been fully defined. The present study identified the functional implications of miR‑181 expression during renal fibrosis. miR‑181 exhibited significantly reduced expression in the serum of renal fibrosis patients and in the kidneys of mice with unilateral ureteral obstruction (UUO). In addition, miR‑181 downregulated the expression of human α‑smooth muscle actin (α‑SMA) in response to angiotensin II stimulation. Transfection with miR‑181 mimics significantly suppressed the expression levels of α‑SMA, connective tissue growth factor, collagen type I α1 (COL1A1) and collagen type III α1 (COL3A1) in NRK49F cells. Notably, early growth response factor‑1 (Egr1) was identified as a direct target gene of miR‑181. Furthermore, in vivo experiments revealed that treatment with miR‑181 agonist strongly rescued kidney impairment induced by UUO, as supported by Masson's trichrome staining of kidney tissues and reverse transcription‑quantitative polymerase chain reaction analysis of COL1A1 and COL3A1 mRNA levels. Therefore, miR‑181 may be regarded as an important mediator in the control of profibrotic markers during renal fibrosis via binding to Egr1, and may be a promising new target in the diagnosis and therapy of renal fibrosis.

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