Zinc finger protein 281 inhibits high glucose-induced epithelial-mesenchymal transition and extracellular matrix synthesis in renal tubular epithelial cells
- VernacularTitle:锌指蛋白281抑制高糖诱导的肾小管上皮细胞上皮间质转化和细胞外基质合成
- Author:
Weiling HOU
1
;
Yunyang QIAO
;
Xiaoyun WU
;
Huimin SHI
;
Gaoting QU
;
Aiqing ZHANG
Author Information
- Keywords: diabetic nephropathies; tristetraprolin; epithelial-mesenchymal transition; extracellular matrix; AMP-activated protein kinases; tubulointerstitial fibrosis; zinc finger protein 281
- From: Tianjin Medical Journal 2024;52(7):720-726
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the role and mechanism of zinc finger protein 281(ZNF281)in high glucose(HG)-induced epithelial-mesenchymal transition(EMT)and extracellular matrix(ECM)synthesis in renal tubular epithelial cells(RTECs).Methods HG induced RTECs were used to construct a diabetic kidney disease cell model,and cells were divided into the control group,the HG group and the mannitol group.Cell proliferation viability was detected by CCK-8.The expression of ZNF281 was knocked down in HG-treated RTECs using small interfering RNA(siRNA).HG-induced RTECs after knockdown of ZNF281 were divided into the control group,the HG group,the HG+ZNF281 siRNA group and the HG+ZNF281 vector group.Adenosine monophosphate-activated protein kinase(AMPK)was activated using AMPK agonist,acadexin(AICAR),and then cells were divided into the control group,the HG group,the HG+AICAR group and the HG+dimethyl sulfoxide group.The expression levels of ZNF281,EMT and ECM synthesis-related indexes were detected by qPCR and Western blot assay.Results Compared with the control group,the protein and mRNA expression levels of vimentin,α-smooth muscle actin(α-SMA),fibronectin(FN)and collagen Ⅰ(Col Ⅰ)were significantly higher,and the expression of E-cadherin was significantly lower in the HG group.Compared with the HG group,the protein and mRNA expression levels of EMT and ECM synthesis-related indexes were significantly changed in the HG+ZNF281 siRNA group and the HG+AICAR group.The protein and mRNA expression levels of ZNF281 were significantly reduced in the HG+AICAR group compared with the HG group.In cells co-treated with AICAR and transfected with ZNF281 plasmid,the expression levels of vimentin,α-SMA,FN and Col Ⅰ were significantly higher in the AICAR+ZNF281 group,and E-cadherin was significantly lower compared with that of the vector group.Conclusion AMPK inhibits EMT and ECM synthesis in HG-treated RTECs by negatively regulating the expression level of ZNF281.
