Acute kidney injury (AKI), commonly occurring as complications of sepsis, cardiac surgery, and liver or kidney transplantation, is a critical care syndrome. It is well known that lipopolysaccharide (LPS) shock is a common triggering factor for AKI. This study is aimed to examine the effect of flavonoid compound hispidulin on LPS-induced AKI. For this, renal tubular epithelial cell HK-2 was treated with LPS to establish an in vitro model of AKI. The effect of hispidulin on HK-2 cell viability was examined using CCK-8 assay. Cell apoptosis was determined by TUNEL and flow cytometry. Apoptosis marker proteins were determined by using western blot. The levels of pro-inflammatory cytokines were determined by ELISA assay and qRT-PCR. The translocation of NF-κB was determined by western blot. The effect of MyD88 on the cytoprotective activities of hispidulin was examined by overexpressing MyD88 in HK-2 cells. Our results showed that hispidulin was not able to produce a cytotoxic effect on HK-2 cells at tested concentrations.However, hispidulin could protect HK-2 cells from LPS-induced cell injury. Our results also showed that hispidulin was able to attenuate LPS-induced HK-2 cell apoptosis. In addition, LPS led to an inflammatory response in HK-2 cells, evidenced by NF-κB p65 activation as well as increased expression and release of inflammatory cytokine IL-6 and TNFα, which could be reversed by pretreatment with hispidulin. Overexpression MyD88 was found to significantly dampen the cytoprotective activities of hispidulin against LPS insult. More importantly, MyD88 was identified as a direct target of hsa-miR-203, and hispidulin was found to regulate the expression of MyD88 via upregulating hsa-miR-203. Our results showed that hispidulin attenuates LPS-induced HK-2 damage via regulating hsa-miR-203/MyD88 axis.
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