MiR-6835 promoted LPS-induced inflammation of HUVECs associated with the interaction between TLR-4 and AdipoR1 in lipid rafts.

• Main Authors: Jiao Liu, Guang Li, Chuang Chen, Dechang Chen, Qingshan Zhou
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2017-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC5708807?pdf=render

High mortality rate of critically-ill patients could be induced by sepsis and septic shock, which is the extremely life threatening. The purpose of this work is to identify and evaluate the potential regulatory mechanism of LPS-induced inflammation associated with miR-6835 and lipid rafts in HUVECs.The 3' UTR luciferase activity of AdipoR1 was detected, which was predicted the potential target gene of miR-6835. Moreover, the treated HUVECs with or without inhibitors or mimics of miR-6835 were used. Furthermore, the bio-functions of HUVECs were explored. The protein expression levels of SIRT-1, AMPK, and AdipoR1 were assessed, which were involved in the AdipoR1 signaling pathway. Then, the interaction between TLR-4 and AdipoR1 in lipid rafts and its mediation role on LPS-induced inflammation was investigated in HUVECs.MiR-6835 targeted directly on AdipoR1, and suppressed its expression in mRNA (mimics of miR-6835: 0.731±0.016 vs control: 1.527±0.015, P<0.001) and proteins levels, then regulated protein expression of SIRT-1 and AMPK, which were the downstream target genes of AdipoR1 signaling pathway. MiR-6835 enhanced LPS-induced inflammation process in HUVECs (TNF-α: LPS+mimics of miR-6835: 1638.51±78.43 vs LPS: 918.73±39.73, P<0.001; IL-6: LPS+mimics of miR-6835: 1249.35±69.51 vs LPS: 687.52±43.64, P<0.001), which was associated with the interaction between TLR-4 and AdipoR1 in lipid rafts.MiR-6835 is the key regulator of LPS-induced inflammation process in HUVECs. The interaction between TLR-4 and AdipoR1 mediated by lipid rafts at membrane of HUVECs with inflammation process induced by miR-6835. Our results demonstrated a hopeful strategy for treatment on sepsis by aiming at lipid rafts and miR-6835.