Lack of miRNA-17 family mediates high glucose-induced PAR-1 upregulation in glomerular mesangial cells.
Naunyn Schmiedebergs Arch Pharmacol
; 395(1): 77-85, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34792626
ABSTRACT
Upregulation 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 upregulation 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 upregulated 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 significantly 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 downregulated in both high glucose-cultured HMCs and equivalent osmotic press control compared with normal glucose culture. So miR-20a was selected to confirm the role of miR-17 family on PAR-1 upregulation, finding that miR-20a-5p overexpression reversed the upregulation of PAR-1 in mRNA and protein levels induced by high glucose in HMCs. In summary, our finding indicated that PAR-1 upregulation mediated proliferation of glomerular mesangial cells induced by high glucose, and deficiency of miR-17 family resulted in PAR-1 upregulation.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Receptor PAR-1
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Células Mesangiais
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article