Lack of miRNA-17 family mediates high glucose-induced PAR-1 up-regulation in glomerular mesangial cells
| Autor: | Xiao-Fei An, Yao-Wu Liu, Ling-Shan Gou, Zhuang-Zhuang Tang, Pan-Pan Gu |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Pyridines Glomerular Mesangial Cell Down-Regulation Cell Line Diabetic nephropathy Lactones Thrombin Downregulation and upregulation Internal medicine microRNA Thrombin receptor medicine Humans Diabetic Nephropathies Receptor PAR-1 Receptor Cell Proliferation Pharmacology Cell growth Chemistry General Medicine medicine.disease Up-Regulation MicroRNAs Endocrinology Glucose Mesangial Cells medicine.drug |
| Popis: | Up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) is verified to contribute to chronic kidney diseases, including diabetic nephropathy, however, the mechanisms are still unclear. In this study, we investigated the effect of PAR-1 on high glucose-induced proliferation of human glomerular mesangial cells (HMCs), and explored the mechanism of PAR-1 up-regulation from alteration of microRNAs. We found that high glucose stimulated proliferation of the mesangial cells whereas PAR-1 inhibition with vorapaxar attenuated the cell proliferation. Moreover, high glucose up-regulated PAR-1 in mRNA level and protein expression while did not affect the enzymatic activity of thrombin in HMCs after 48 h culture. Then high glucose induced PAR-1 elevation was likely due to the alteration of the transcription or post-transcriptional processing. It was found that miR-17 family members including miR-17-5p, -20a-5p, and − 93-5p were markedly decreased among the eight detected microRNAs only in high glucose-cultured HMCs, but miR-129-5p, miR-181a-5p, and miR-181b-5p were markedly decreased in both high glucose-cultured HMCs and osmotic press control compared with normal glucose culture. So miR-20a was selected to confirm the role of miR-17 family on PAR-1 up-regulation, finding that miR-20a-5p overexpression reversed the up-regulation of PAR-1 in mRNA and protein levels induced by high glucose in HMCs. In summary, our finding indicated that PAR-1 up-regulation mediated proliferation of glomerular mesangial cells induced by high glucose, and deficiency of miR-17 family resulted in PAR-1 up-regulation. |
| Databáze: | OpenAIRE |
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