Effect of histone acetylate modification on the plasminogen activator inhibitor 1 gene regulation in mesangial cells
10.3760/cma.j.issn.1001-7097.2012.11.013
- VernacularTitle:组蛋白乙酰化修饰对系膜细胞内纤溶酶原激活物抑制物1基因表达的影响
- Author:
Nian LIU
;
Yingchun CUI
;
Guangdong SUN
;
Hang YUAN
;
Ping LUO
;
Lining MIAO
- Publication Type:Journal Article
- Keywords:
Histones;
Acetylation;
Transforming growth factor β1;
Plasminogen activator inhibitor 1;
Mesangial cells
- From:
Chinese Journal of Nephrology
2012;(11):883-887
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of histone acetylation change on the transforming growth factor β1 (TGF-β 1)-associated plasminogen activator inhibitor 1 (PAI-1) regulation in mesangial cells (MCs).Methods MCs were transfected with histone acetyltransferase (HAT)CREB-binding protein(CBP),P300 or histone deacetylase (HDAC) 1,3,5 expression vectors,followed by luciferase assay,real-time PCR and Western blotting to see the change of PAI-1 gene's transcriptional activity,mRNA and protein in response to TGF-β1.HDAC inhibitor trichostatin A(TSA)was used and TGF-β1-Smad signaling activity was detected also in this experiment.Results TGF-β1 enhanced PAI-1 transcriptional activity and mRNA expression (P ＜ 0.05).Over-expression of CBP or P300 significantly increased TGF-β1-associated PAI-1 transcriptional activity,mRNA and protein expression (P ＜ 0.05).On the contrary,over-expression of HDAC1,3,5 or dominant negative CBP or dominant negative P300 obviously reduced PAI-1 gene's expression induced by TGF-β1 (P ＜ 0.05).Change of HAT/HDAC did not affect TGF-β1-associated Smad2/3 phosphorylation.TSA enhanced TGF -β1 induced PAI-1 gene's regulation markedly,but did not change TGF-β1-Smad2/3 signaling activity.Conclusion Change of histone acetylation can affect TGF-β1 associated PAI-1 gene's regulation in MCs.
