High glucose upregulates PAR‐1 in SH‐SY5Y cells via deficiency of miR‐20a and miR‐190a
| Autor: | Li Kong, Pan‐Pan Gu, Zhuang‐Zhuang Tang, Ling‐Shan Gou, Yao‐Wu Liu |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Fundamental & Clinical Pharmacology. 36:509-517 |
| ISSN: | 1472-8206 0767-3981 |
| DOI: | 10.1111/fcp.12743 |
| Popis: | Thrombin activity enhancement and its receptor protease-activated receptor 1 (PAR-1) activation play vital roles in neurologic deficits in the central nervous system. Our recent study showed that PAR-1 upregulation stimulated by chronic high glucose (HG) caused central neuron injury through neuroinflammation; however, the molecular mechanisms are far from clear. In the present study, we found that HG resulted in neuronal injury of SH-SY5Y cells as evidenced by decreased cell viability and increased lactate dehydrogenase release and elevated the mRNA level of PAR-1. Moreover, we predicted and determined several potential microRNAs (miRs) combining with the 3'-UTR of PAR-1 mRNA, finding that miR-20a-5p, miR-93-5p, and miR-190a-5p were significantly decreased in HG-cultured SH-SY5Y cells compared with control. Further, SH-SY5Y cells stably transfected with miR-20a-5p or miR-190a-5p mimic were established, and overexpression efficiency were confirmed. It was found that miR-20a-5p or miR-190a-5p overexpression markedly decreased PAR-1 mRNA level and protein expression in SH-SY5Y cells cultured with HG and normal glucose, indicating that miR-20a or miR-19a deficiency contributed to HG-induced PAR-1 upregulation. Together, our findings demonstrated that PAR-1 upregulation mediated HG-induced neuronal damage in central neurons, which was achieved through miR-20a or miR-190a deficiency. |
| Databáze: | OpenAIRE |
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