Transforming growth factor-β1-induced podocyte injury is associated with increased microRNA-155 expression, enhanced inflammatory responses and MAPK pathway activation

转化生长因子-β1诱导的足细胞损伤与microRNA-155表达增加、炎症反应增强和MAPK通路激活有关

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作者:Xintong Zheng, Qiuhong Zhong, Xu Lin, Xianjun Gu, Xiaoyan Ling, Zhao Liang, Qing Qin, Xiuri Du

Abstract

MicroRNA-155 (miR-155) is associated with various diseases. However, the potential role of miR-155 in early glomerular disease (EGD) remains elusive. In the present study, the clinical significance of urinary miR-155 expression was explored in patients with EGD using receiver operating characteristic curve analysis. Conditionally immortalized mouse podocytes were cultured in vitro and treated with transforming growth factor-β1 (TGF-β1) at different concentrations and durations. The gene expression levels of mRNAs and miR-155 were detected using reverse transcription-quantitative PCR. Synaptopodin, CD2-associated protein (CD2AP), p38, and extracellular signal-regulated kinase (Erk) 1/2 expressions were detected using western blotting. Cell supernatants were collected for assaying tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations using enzyme-linked immunosorbent assay. The Pearson correlation analysis was used to analyze the correlation between miR-155 levels and TNF-α or IL-6. It was found that miR-155 levels in urine have high sensitivity and specificity in the diagnosis of EGD. Time- and dose-dependent TGF-β1 treatments downregulated synaptopodin and CD2AP expression levels, and activated the p38 and Erk 1/2 pathway. However, these effects were attenuated by p38 and Erk 1/2 phosphorylation inhibitors. Additionally, TNF-α and IL-6 secretions were elevated, and their concentrations were positively correlated with the expression of miR-155 during podocyte injury. Thus, the present study indicated that miR-155 is a potential biomarker for the diagnosis of EGD, and its expression is associated with the release of pro-inflammatory cytokines and activation of mitogen-activated protein kinase (MAPK) pathway in TGF-β1-induced podocyte injury. The present study suggests that the TGF-β1/miR-155/MAPK axis is a novel target in the mechanism of EGD.

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