Transforming growth factor‑β1‑induced podocyte injury is associated with increased microRNA‑155 expression, enhanced inflammatory responses and MAPK pathway activation
| Autor: | Xiuri Du, Xintong Zheng, Zhao Liang, Xiaoyan Ling, Xu Lin, Qiuhong Zhong, Qing Qin, Xianjun Gu |
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| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
Cancer Research Oncogene Chemistry Kinase p38 mitogen-activated protein kinases Articles General Medicine MAPK Molecular biology miR-155 Podocyte medicine.anatomical_structure Immunology and Microbiology (miscellaneous) inflammation TGF-β1 medicine Synaptopodin Protein kinase A podocyte injury Transforming growth factor |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-1015 1792-0981 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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