Overexpression of HIC1 plays a protective effect on renal cell injury caused by lipopolysaccharide by inhibiting IL-6/STAT3 pathway

Abstract

Sepsis is a life-threatening condition that can even occur due to an infection. Systemic inflammatory response syndrome acts a pivotal role in acute kidney injury (AKI). Although great advancements have been achieved for treating sepsis-induced AKI, its prognosis and pathophysiology remain unclear. In order to gain insights into the relevant role of hypermethylated in cancer 1 (HIC1) in AKI, a cellular model of AKI caused by sepsis was performed in lipopolysaccharide (LPS)-treated human kidney 2 (HK-2) cell line. The overexpression vector pcDNA3.1-HIC1 was transfected into HK-2 cell line to examine the effects of HIC1 on LPS-treated HK-2 cell line. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot and enzyme-linked immunosorbent assay (ELISA) assays were performed to examine the alterations in the expression levels of HIC1, cell apoptosis, or inflammation-related biomarkers. The apoptotic rate of HK-2 cell line was measured by flow cytometry. This study suggested that LPS treatment downregulated HIC1 and inhibited HK-2 cell viability, whereas HIC1 overexpressing reversed these effects. Importantly, HIC1 has a protective effect on LPS-induced cellular apoptosis and inflammatory response. Moreover, overexpression of HIC1 suppressed the LPS-induced activation of IL-6/STAT3 signaling pathway in HK-2 cell line. HIC1 protects HK-2 cell line against LPS-induced damage, which was partly through the inhibition of IL-6/STAT3 signaling pathways.