Downregulating PDCD4 alleviated the LPS induced inflammation and apoptosis of renal tubular epithelial cells by suppressing the expression of MAR2K3 and p38 MAPK
Jiang Wei
Zhang Yinan
Zhang Jianfeng
Huang Zhongwei
Abstract：Objective To investigate the mechanism of programmed cell death protein 4(PDCD4)in sepsis-associated acute kidney injury(AKI)and its potential therapeutic effects on sepsis-associated AKI by regulating the expression of mitogen-activated protein kinase 3(MAP2K3)and p38 mitogen-activated protein kinase(p38 MAPK).Methods Lipopolysaccharide(LPS)was used to stimulate human renal tubular epithelial cells(HK-2)to induce sepsis-associated AKI.Next,the expression of PDCD4 was knockdown by using RNA interfering in LPS induced HK-2 cells.Commercial kits and TUNEL staining were used for the detection of cellular inflammation,oxidative stress and apoptosis.Then,co-immunoprecipitation assay was performed for the examination of the association between PDCD4 and MAP2K3.The MAP2K3-overexpressing HK-2 cells were constructed,following which their inflammation and apoptosis were determined by using the same aforementioned methods.Results Knockdown of PDCD4 relieved the LPS-induced inflammation,apoptosis and the higher levels of reactive oxygen species in HK-2.The co-immunoprecipitation assays also showed that PDCD4 can interact directly with MAP2K3.The overexpression of MAP2K3 and the application of a p38 MAPK signal agonist abolished the effect of PDCD4 knockdown on the LPS-induced inflammation,apoptosis and oxidative stress of these cells.Conclusions Inhibition of PDCD4 alleviates the LPS-induced inflammation and apoptosis of renal tubular epithelial cells by suppressing the expression of MAP2K3 and p38 MAPK.
Keywords：Acute kidney injurySepsisProgrammed cell death protein 4Mitogen-activated protein kinase 3p38 mitogen-activated protein kinaseReactive oxygen speciesSuperoxide dismutaseMalondialdehyde
Publication Date：2024-04-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：9( 305-313 )