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). CONCLUSION: Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGFβ(1) and downregulation of PPARγ.
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). CONCLUSION:Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGFβ(1) and downregulation of PPARγ.
Authors: Martin Ošt'ádal; Adam Eckhardt; Jan Herget; Ivan Mikšík; Pavel Dungl; Jiří Chomiak; Monika Frydrychová; Michal Burian Journal: Mol Cell Biochem Date: 2014-12-04 Impact factor: 3.396