Tenascin-x facilitates myocardial fibrosis and cardiac remodeling through transforming growth factor-β1 and peroxisome proliferator-activated receptor γ in alcoholic cardiomyopathy

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-beta 1 and peroxisome proliferator-activated receptor gamma (TGF beta 1-PPAR gamma) 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, TGF beta 1, smad-7 and PPAR gamma 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 TGF beta(1) protein expression levels were higher in group A, while smad-7 and PPAR gamma 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 PPAR gamma, and positively correlated with LVEDd, CVF, smad-3, and TGF beta(1) (P < 0.001). Conclusion Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGF beta(1) and downregulation of PPAR gamma. Chin Med J 2011;124(3):390-395