SUMO protease SENP1 acts as a ceRNA for TGFBR2 and thus activates TGFBR2/Smad signaling responsible for LPS-induced sepsis
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...
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doaj-8e127aa9e76042e69277aa2932489aad2021-05-20T07:37:05ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-04-01112SUMO protease SENP1 acts as a ceRNA for TGFBR2 and thus activates TGFBR2/Smad signaling responsible for LPS-induced sepsisChao Zhang0Jing Li1Xiaosong Qiu2Yuzhu Chen3Xin Zhang4Department of Intensive Medicine (ICU), Hongze Huaian District People’s Hospital, No. 102, Dongfeng road, Hongze District, Huaian 223100, ChinaDepartment of Anesthesia, The Second Affiliated Hospital of Xuzhou Medical University, No. 32, Meijian road, Xuzhou 221000, China; Corresponding author.Department of EICU, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, ChinaDepartment of Intensive Medicine (ICU), Hongze Huaian District People’s Hospital, No. 102, Dongfeng road, Hongze District, Huaian 223100, ChinaDepartment of Intensive Medicine (ICU), Hongze Huaian District People’s Hospital, No. 102, Dongfeng road, Hongze District, Huaian 223100, ChinaThis 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.http://www.sciencedirect.com/science/article/pii/S0753332218381903SepsisSENP1TGFBR2Smad2/3LPS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chao Zhang Jing Li Xiaosong Qiu Yuzhu Chen Xin Zhang |
spellingShingle |
Chao Zhang Jing Li Xiaosong Qiu Yuzhu Chen Xin Zhang SUMO protease SENP1 acts as a ceRNA for TGFBR2 and thus activates TGFBR2/Smad signaling responsible for LPS-induced sepsis Biomedicine & Pharmacotherapy Sepsis SENP1 TGFBR2 Smad2/3 LPS |
author_facet |
Chao Zhang Jing Li Xiaosong Qiu Yuzhu Chen Xin Zhang |
author_sort |
Chao Zhang |
title |
SUMO protease SENP1 acts as a ceRNA for TGFBR2 and thus activates TGFBR2/Smad signaling responsible for LPS-induced sepsis |
title_short |
SUMO protease SENP1 acts as a ceRNA for TGFBR2 and thus activates TGFBR2/Smad signaling responsible for LPS-induced sepsis |
title_full |
SUMO protease SENP1 acts as a ceRNA for TGFBR2 and thus activates TGFBR2/Smad signaling responsible for LPS-induced sepsis |
title_fullStr |
SUMO protease SENP1 acts as a ceRNA for TGFBR2 and thus activates TGFBR2/Smad signaling responsible for LPS-induced sepsis |
title_full_unstemmed |
SUMO protease SENP1 acts as a ceRNA for TGFBR2 and thus activates TGFBR2/Smad signaling responsible for LPS-induced sepsis |
title_sort |
sumo protease senp1 acts as a cerna for tgfbr2 and thus activates tgfbr2/smad signaling responsible for lps-induced sepsis |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-04-01 |
description |
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. |
topic |
Sepsis SENP1 TGFBR2 Smad2/3 LPS |
url |
http://www.sciencedirect.com/science/article/pii/S0753332218381903 |
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