科研之友
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摘要
Objective. The present study was performed to investigate the effects and mechanisms of miR-99a on LPS-induced endothelial cell inflammation, as well as the regulation of NF-kappa B on miR-99a production. Methods and Results. ELISA showed that LPS treatment significantly promoted the secretion of inflammatory factors (TNF-alpha, IL-6, IL-1 beta, and MCP-1). LPS treatment also inhibited miR-99a production and promoted mTOR expression and NF-kappa B nuclear translocation. Overexpression of miR-99a suppressed the LPS-induced TNF-alpha, IL-6, IL-1 beta, and MCP-1 overproduction, mTOR upregulation, and NF-kappa B nuclear translocation. The PROMO software analysis indicated NF-kappa B binding site in the -1643 to -1652 region of miR-99a promoter. Dual luciferase reporter analysis, electrophoretic mobility shift assays (EMSA), and chromosome immunoprecipitation (ChIP) assays demonstrated that NF-kappa B promoted the transcription of miR-99a by binding to the -1643 to -1652 region of miR-99a promoter. Further studies on HUVECs verified the regulatory effects of NF-kappa B on miR-99a production. Conclusion. MiR-99a inhibited the LPS-induced HUVECs inflammation via inhibition of the mTOR/NF-kappa B signal. NF-kappa B promoted miR-99a production by binding to the -1643 to -1652 region of miR-99a promoter. Considering the importance of endothelial inflammation on cardiovascular diseases, such as atherosclerosis, our results may provide a new insight into the pathogenesis and therapy of atherosclerosis.
