Abstract

This study aims to explore the roles and related mechanisms of SUMO protease SENP1 in sepsis. Here, RNA-sequencing assay showed that SENP1 was significantly increased in human umbilical vein endothelial cells (HUVECs) with LPS treatment. Gene set enrichment analysis (GSEA) of RNA-sequencing dataset revealed that a positive enrichment of inflammation signatures was observed in HUVECs with SENP1 3′UTR overexpression. Further functional annotation analysis revealed that SENP1 3′UTR overexpression was positively correlated with TGFBR2 signaling pathway. Mechanistically, TGFBR2 was identified as a ceRNA (competing endogenous RNA) target of SENP1 and the downstream effectors Smad2/3 were also overexpressed in HUVECs with SENP1 3′UTR overexpression. Injection of SENP1 siRNA following LPS treatment attenuated LPS-induced sepsis, evidenced by the downregulation of IL-2 and TNF-α secretion and prolonged the overall survival of septic mice. Consistent results were obtained in vitro. Additionally, TGFBR2 overexpression partially abrogated SENP1 siRNA-mediated inhibition on LPS-induced sepsis. Thus, these results suggest that SENP1 promotes sepsis via activating the TGFBR2 signaling.