Role of transforming growth factor β1 in the process of histone acetylate modification of plasminogen activator inhibitor 1 gene in mesangial cells / 中华肾脏病杂志

ABSTRACT

Objective To explore the effect of transforming growth factor β1 (TGF-β1) on epigenetic histone lysine acetylation in the plasminogen activator inhibitor 1 (PAI-1) promoter and transcribe regions in glomerular mesangial cells (GMCs).Methods Chromatin immunoprecipitation assay and real-time quantitative PCR were used to detect Histone3K9 acetylation (H3K9Ac) in the PAI-1 promoter and transcribe regions induced by TGF-β1 and high glucose.Immunoprecipitation was also used to see the cooperation of Smad3,CBP and Sp1 proteins.Results In the four target regions of PAI-1 promoter,TGF-β1 treatment enhanced H3K9Ac at P1,P2 and P3 in GMCs (P ＜ 0.05),but no change was seen in the P4 region which was far from the transcription starting site.TGF-β1 obviously induced H3K9Ac in the T1 transcribe region of PAI-1 instead of T2 (P ＜ 0.05).High glucose increased PAI-1 mRNA expression and H3K9Ac around P1 promoter region (P＜ 0.05).TGF-β1 neutralizing antibody abrogated high glucose-induced H3K9Ac at PAI-1 promoter (P ＜ 0.01).TGF-β1 treatment could recruit Smad3 and CBP protein binding to the PAI-1 promoter regions (P1,P2,P3),and induce their cooperation in GMCs,which were responsing to TGF-β1 associated H3K9Ac.Conclusion TGF-β1 can induce H3K9Ac in the promoter and transcribe regions of PAI-1,promote Smad3 recruition and cooperation with Sp1 and CBP,which are associated with PAI-1 gene's regulation in GMCs.