Cytoprotective Effect of Heat Shock Protein 27 Against Lipopolysaccharide-Induced Apoptosis of Renal Epithelial HK-2 Cells

Abstract

Background:In response to various stimuli, heat shock protein 27 (Hsp27) functions as an anti-apoptotic or/and anti-inflammatory factor which confers a survival advantage to cells. This study was aimed to explore whether Hsp27 also has a cytoprotective role in human renal tubular epithelial cells, and to evaluate its potential in treating septic acute kidney injury (septic AKI). Methods: HK-2 cells were subjected to different concentrations (0-10 μg/mL) of lipopolysaccharide (LPS) for various times (0-24 h) to establish a septic AKI model in vitro. Before LPS administration, HK-2 cells were transfected either with vectors or siRNA against Hsp27, and the changes in cell viability and apoptotic cells rate were assessed using CCK-8 and flow cytometry. The expression changes in apoptosis-related proteins, proinflammatory cytokines and chemokine, as well as main factors in NF-κB and JNK pathways were mainly determined by Western blotting. Besides, the relationship between Hsp27 and Bcl-2 was detected by co-immunoprecipitation. Results: LPS remarkably damaged HK-2 cells by reduction of cell viability, induction of apoptosis, and stimulation of proinflammatory cytokines and chemokine release. Hsp27 overexpression significantly impaired LPS-induced damage in HK-2 cells. Hsp27 overexpression couldn't alter the mRNA level of Bcl-2, but could interact with Bcl-2 at an endogenous level. Both NF-κB and JNK pathways were activated by LPS, while were blocked in Hsp27-overexpressing cells. Conclusion: Hsp27 overexpression conferred a survival advantage to LPS-injured HK-2 cells by controlling cell viability, apoptosis and inflammation, possibly via interaction with Bcl-2 and modulation of NF-κB and JNK pathways.

LncRNA TapSAKI promotes inflammation injury in HK-2 cells and urine derived sepsis-induced kidney injury

“…To further explore the mechanism of lncRNA TapSAKI in sepsis‐induced kidney injury, PTEN and TLR4/NF‐κB signaling pathway were focused in LPS‐treated HK‐2 cells. LPS is the component of the cell wall of Gram‐negative bacteria, and studies have proved it is closely related to renal tubular epithelial cell apoptosis . Besides, the apoptosis of renal tubular epithelial cell is considered as an important cause of septic acute kidney injury .…”

“…LPS is the component of the cell wall of Gram-negative bacteria, and studies have proved it is closely related to renal tubular epithelial cell apoptosis. [4,20] Besides, the apoptosis of renal tubular epithelial cell is considered as an important cause of septic acute kidney injury. [21] So, we considered HK-2 cell apoptosis as an indicator for septic acute kidney injury.…”

“…Therefore, it is necessary to find effective therapeutic targets for sepsis‐induced kidney injury. As is well known, lipopolysaccharide (LPS), a component of the cell wall of gram‐negative bacteria, is related with the apoptosis of renal tubular epithelial cells and acute kidney injury . Reports have shown that LPS is commonly used in the induction of apoptosis in vivo and in vitro models of acute kidney injury …”

“…As is well known, lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, is related with the apoptosis of renal tubular epithelial cells and acute kidney injury. [4] Reports have shown that LPS is commonly used in the induction of apoptosis in vivo and in vitro models of acute kidney injury. [5,6] Phosphatase and tension homology deleted on chromosome 10 (PTEN) is a classic tumor suppressor and the most important negative regulator of the PI3K signaling pathway.…”

BCL6 attenuates renal inflammation via negative regulation of NLRP3 transcription

“…The concentration of Ang II or LPS was selected according to previous studies. In Ang II-induced inflammation model, HK-2 cells were treated with 1 μ M of Ang II or PBS for 12 h. 44 , 46 In LPS-induced inflammation model, HK-2 cells were treated with 5 μ g/ml of LPS or PBS for 8 h. 47 , 48 …”