The role of GATA4 in Cr(Ⅵ)-induced premature senescence in hepatocytes
Objective To investigate the role played by GATA4 in regulating premature senescence by constructing a Cr(Ⅵ)-induced prematurely senescent L02 hepatocyte model.Methods L02 hepatocytes were continuously treated with 10 nmol/L Cr(Ⅵ).β-Gal staining and Western blot were used to detect senescence-related protein expression to clarify the onset of premature senescence in L02 hepatocytes.The effect of GATA4 on cellular senescence was investigated by constructing GATA4-sh L02 hepatocytes and their control cells with Cr(Ⅵ)staining.β-Gal staining and Western blot were used to detect the expression of senescence-associated proteins,and it was clear that GATA4 could promote the premature senescence of L02 hepatocytes induced by Cr(Ⅵ).Results After 10 nmol/L Cr(Ⅵ)treatment of L02 hepatocytes for 4 weeks,β-Gal staining showed a large number of positive senescent cells and the expressions of senescence-related proteins FN1,CLU and SMP30 were significantly increased(LSD-t=5.52,10.39,11.66,P＜0.05).The expressions of GATA4,TRAF3IP2 and p65,proteins related to GATA4/NF-κB pathway,were significantly increased(LSD-t=12.13,16.64,13.73,P＜0.05).When GATA4 was knocked down after 10 nmol/L Cr(Ⅵ)treatment of GATA4-sh L02 hepatocytes,the expression of senescence-associated proteins was significantly lower compared with the control group(t=15.30,P＜0.05).Conclusion Cr(Ⅵ)induces premature senescence in L02 hepatocytes via GATA4.
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