title: Epigenetic factors MeCP2 and HDAC6 control α-tubulin acetylation in cardiac fibroblast proliferation and fibrosis.
abstract: OBJECTIVE
  Cardiac fibrosis is an important pathological feature of cardiac remodeling in heart diseases. Methyl-CpG-binding protein 2 (MeCP2) is a transcription inhibitor, and plays a key role in the fibrotic diseases. However, the precise role of MeCP2 in cardiac fibrosis remains unclear. α-tubulin plays an essential role in cell function, whereby the acetylation state of α-Tubulin dictates the efficiency of cell proliferation and differentiation. This study was undertaken to investigate that MeCP2 dynamics affect the acetylation state of α-tubulin in the cardiac fibrosis.
  
  
  METHODS
  Forty adult male Sprague-Dawley (SD) rats were randomly divided into two groups, cardiac fibrosis was produced by common ISO. Cardiac fibroblasts (CFs) were harvested from SD neonate rats and cultured. The expression of HDAC6, MeCP2, α-SMA, collagen I was measured by western blotting and qRT-PCR. siRNA of HDAC6 and MeCP2 effect the proliferation of cardiac fibroblasts, and affect the acetylation state of α-tubulin.
  
  
  RESULTS
  We have found the acetylation state of α-tubulin in cardiac fibroblasts as well as cardiac tissue from a ISO-induced rat cardiac fibrosis model and observed a reduction in acetylated α-tubulin and an increase in the α-tubulin-specific deacetylase, histone deacetylase 6 (HDAC6). Furthermore, we have shown that treatment of cardiac fibroblasts with HDAC6 inhibitor Tubastatin A and HDAC6-siRNA can restore α-tubulin acetylation levels. In addition, treatment of cardiac fibroblasts with MeCP2-siRNA blocked cell proliferation. Knockdown of MeCP2 suppresses HDAC6 expression in activated cardiac fibroblasts but increases the acetylation of α-tubulin.
  
  
  CONCLUSIONS
  We demonstrated that MeCP2 may negatively control the acetylation of α-tubulin through HDAC6 in cardiac fibroblast proliferation and fibrosis. This study indicated that MeCP2 could be a potentially new therapeutic option for cardiac fibrosis.
authors.affiliation: Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei, 230601, China.|Cardiovascular Research Center, Anhui Medical University, Hefei, 230601, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Pharmacology, The Second Hospital of Anhui Medical University, Hefei, China. yjjncs01@126.com.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei, 230601, China.|Cardiovascular Research Center, Anhui Medical University, Hefei, 230601, China.
authors.forename: Kai-Hu
authors.initials: KH
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui, 230032, China. yncs01@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000107:Acetylation; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000077214:Becaplermin; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D057890:Epigenomics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005355:Fibrosis; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D007545:Isoproterenol; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000378:metabolism*
chemical_list: D000199:Actins; D000077214:Becaplermin; D024042:Collagen Type I; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D007545:Isoproterenol; D051783:Methyl-CpG-Binding Protein 2; D020574:Proto-Oncogene Proteins c-sis; D014404:Tubulin; C497394:Mecp2 protein, rat; C545556:HDAC6 protein, rat; C498862:Acta2 protein, rat
keywords: Cardiac fibroblasts; Histone deacetylase 6; Methyl-CpG-binding protein 2