Overexpression of HIC1 plays a protective effect on renal cell injury caused by lipopolysaccharide by inhibiting IL-6/STAT3 pathway
Xiang Yang, Jianfeng Gong, Xiaosheng Cai, Youjun Yuan, P Arina, M Singer, L Schlapbach, J Trck, T Roger, P Mayeux, L Macmillan-Crow, S Gonsalez, A Corts, Rcd Silva, J Lowe, M Prieto, Silva Lara, L, A Zarjou, A Agarwal, L White, H Hassoun, R Tan, C Wang, C Deng, X Zhong, Y Yan, Y Luo, R Inagi, H Gomez, C Ince, De Backer, D Pickkers, P Payen, D Hotchkiss, J, C Fleuriel, M Touka, G Boulay, C Gurardel, B Rood, D Leprince, V Briones, S Chen, A Riegel, R Lechleider, R Tseng, C Lee, H Hsu, C Tzao, Y Wang, M Kim, B Jeon, D Koh, K Kim, S Park, Yun Co, B Hu, K Zhang, S Li, H Li, Z Yan, L Huang, S Zeng, X Wu, X Chen, H Xu, T Zhang, Y Xu, K Shuai, J Yang, G Stark, R Morris, N Kershaw, J Babon, S Sirkisoon, R Carpenter, T Rimkus, Anderson Harrison, A Lange, A, N Unver, F Mcallister, L Wang, L Cao, H Wang, B Liu, Q Zhang, Z Meng, F Ning, H Zheng, H Tian, T Wang, D Hao, S Han, Y Li, M Yao, T Wu, L Zhang, Y Wang
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.