title: Tenascin-x facilitates myocardial fibrosis and cardiac remodeling through transforming growth factor-β1 and peroxisome proliferator-activated receptor γ in alcoholic cardiomyopathy.
abstract: BACKGROUND
  Tenascin-x, an extracellular matrix glycoprotein exclusively expressed in fibroblasts, can mediate fibrosis in the presence of collagen. Therefore, we have investigated its potential role in facilitating myocardial fibrosis and cardiac remodeling via the transforming growth factor-β1 and peroxisome proliferator-activated receptor γ (TGFβ(1)-PPARγ) pathway in alcoholic cardiomyopathy (ACM).
  
  
  METHODS
  Experimental animals were divided into control (group A) and tenascin-x knock-out groups (group B) receiving alcohol. Six months post treatment, cardiac ejections fraction (EF), fractional shortening (FS), left ventricle end-diastole internal diameter (LVEDd) and collagen column fraction (CVF) were observed. Tenascin-x, smad-3, TGFβ(1), smad-7 and PPARγ protein expression levels were detected by Western blotting.
  
  
  RESULTS
  Six months post treatment, EF and FS values were higher in group B than in group A (P < 0.05 and P < 0.01, respectively), while LVEDd and CVF were lower in group B (P < 0.05 and P < 0.01, respectively). Tenascin-x, smad-3 and TGFβ(1) protein expression levels were higher in group A, while smad-7 and PPARγ levels were lower than in group B (P < 0.01), as measured by immunohistochemistry and Western blotting. Tenascin-x protein expression was negatively correlated with EF, FS, smad-7 and PPARγ, and positively correlated with LVEDd, CVF, smad-3, and TGFβ(1) (P < 0.001).
  
  
  CONCLUSIONS
  Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGFβ(1) and downregulation of PPARγ.
authors.affiliation: Department of Cardiology, First Clinical College of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jing
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhou
authors.forename: Feng-Min
authors.initials: FM
authors.lastname: Zhang
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Sang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002310:Cardiomyopathy, Alcoholic / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D051900:Smad3 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D047495:PPAR gamma; D051900:Smad3 Protein; D051906:Smad7 Protein; D019063:Tenascin; D053773:Transforming Growth Factor beta1; C081865:tenascin X