@Article{biocell.2021.013027,
AUTHOR = {SICONG WANG, RUIJIN LIU, QIUYUAN HAN, KAIJIANG YU},
TITLE = {HSA-MIR-203/MyD88 axis mediates the protective effect of hispidulin on LPS-induced apoptosis in a human renal tubular epithelial line, HK-2},
JOURNAL = {BIOCELL},
VOLUME = {46},
YEAR = {2022},
NUMBER = {1},
PAGES = {149--158},
URL = {http://www.techscience.com/biocell/v46n1/44764},
ISSN = {1667-5746},
ABSTRACT = {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 <i>in vitro</i> 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 TNF-
α, 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.},
DOI = {10.32604/biocell.2021.013027}
}