HuR induces inflammatory responses in HUVECs and murine sepsis via binding to HMGB1

Wang,Jian; Zhao,Ling; Li,Yong; Feng,Shunyi; Lv,Guangxin

doi:10.3892/mmr.2017.8010

HuR induces inflammatory responses in HUVECs and murine sepsis via binding to HMGB1

Authors:
- Jian Wang
- Ling Zhao
- Yong Li
- Shunyi Feng
- Guangxin Lv
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Affiliations: Department of Emergency, The Cangzhou Central Hospital, Hebei 061001, P.R. China, Department of The Second Osteology, The Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, Hebei 061001, P.R. China
Published online on: November 8, 2017 https://doi.org/10.3892/mmr.2017.8010
Pages: 1049-1056

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Abstract

The aim of the present study was to explore the roles of human antigen R (HuR) in sepsis. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses demonstrated that overexpression of HuR increased the expression of high‑mobility group box 1 (HMGB1) in human umbilical vein endothelial cells (HUVECs). HMGB1 was investigated as a potential target of HuR through bioinformatics and RNA‑immunoprecipitation assays. Furthermore, treatment with HuR small interfering (si)RNA suppressed the lipopolysaccharide (LPS)‑mediated release of HMGB1 and reduced HMGB1‑mediated hyperpermeability and leukocyte migration in HUVECs and in septic mice. In addition, HuR‑siRNA injection reduced cecal ligation and puncture (CLP)‑induced HMGB1 release, reduced production of interleukin 6 and lowered mortality rates. Notably, the promotive effects of HuR overexpression on the inflammatory response were attenuated when HUVECs were co‑treated with HMGB1 short hairpin RNA. Therefore, the present results indicated that the ectopic expression of HuR may induce inflammatory responses and thus sepsis by activating the HMGB1 signaling pathway.

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