Inhibition of XBP1 Alleviates LPS-Induced Cardiomyocytes Injury by Upregulating XIAP through Suppressing the NF-κB Signaling Pathway

Abstract

Cardiomyocytes injury caused by sepsis is a complication of common clinical critical illness and an important cause of high mortality in intensive care unit (ICU) patients. Therefore, lipopolysaccharide (LPS)-induced H9c2 cells were used to simulate the cardiomyocytes injury in vitro. The aim of this study was to investigate whether X-box binding protein 1 (XBP1) exacerbated LPS-induced cardiomyocytes injury by downregulating Xlinked inhibitor of apoptosis protein (XIAP) through activating the NF-κB signaling pathway. After transfection or LPS induction, XBP1 expression was detected by RT-qPCR analysis and Western blot analysis. The viability and apoptosis of H9c2 cells was detected by MTT assay and TUNEL assay. The protein expression related to apoptosis and NF-κB signaling pathway was detected by Western blot analysis. The inflammation and oxidative stress in H9c2 cells was evaluated by their commercial kits. Dual-luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to determine the combination of XBP1 and XIAP. As a result, LPS promoted the XBP1 expression in H9c2 cells. XBP1 was combined with XIAP. Inhibition of XBP1 increased viability, and inhibited apoptosis, inflammation, and oxidative stress of LPS-induced H9c2 cells by suppressing the NF-κB signaling pathway, which was partially reversed by the inhibition of XIAP. In conclusion, inhibition of XBP1 alleviates LPS-induced cardiomyocytes injury by upregulating XIAP through suppressing the NF-κB signaling pathway.

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KS and CZ conceived and designed the experiments and CZ conducted the whole experiment in this study with the help of CW and YR. CW and YR also participated in the data arrangement. CZ wrote the paper and KS corrected the error in the manuscript.

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Correspondence to Kai Sheng.

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Zhang, C., Chen, X., Wang, C. et al. Inhibition of XBP1 Alleviates LPS-Induced Cardiomyocytes Injury by Upregulating XIAP through Suppressing the NF-κB Signaling Pathway. Inflammation (2021). https://doi.org/10.1007/s10753-020-01392-w

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KEY WORDS

  • X-box binding protein 1 (XBP1)
  • Cardiomyocytes injury
  • Xlinked inhibitor of apoptosis protein (XIAP)
  • NF-κB signaling pathway