Tenascins in fibrotic disorders-from bench to bedside

Abstract

Although fibrosis is becoming increasingly recognized as a major cause of morbidity and mortality in chronic inflammatory diseases, available treatment strategies are limited. Tenascins constitute a family of matricellular proteins, primarily modulating interactions of cells with other matrix components and growth factors. Data obtained from tenascin C deficient mice show important roles of this molecule in several models of fibrosis. Moreover there is growing evidence that tenascin C has a strong impact on chronic inflammation, myofibroblast differentiation and recruitment. Tenascin C as well as tenascin X has furthermore been shown to affect TGF-β activation and signaling. Taken together these data suggest that these proteins might be important factors in fibrosis development and make them attractive both as biological markers and as targets for therapeutical intervention. So far most clinical research in fibrosis has been focused on tenascin C. This review aims at summarizing our up-to-date knowledge on the involvement of tenascin C in the pathogenesis of fibrotic disorders.

Keywords: MAP—kinases, Mitogen-activated protein kinases; PI3K, Phosphatidylinositol-4, 5-bisphosphate 3-kinase; PKB, protein kinase B; biomarker; extracellular matrix remodeling; fibrosis; inflammation; tenascin.

Figure 1.

Cellular and molecular mechanisms by which Tenascin C and X influence fibrosis. Tenascin C participates in maintaining a proinflammatory environment and increases migration of fibroblasts and myofibroblasts. Due to their effects on TGF-β signaling pathway, tenascin C and X influence fibroblast and epithelial cells differentiation into myofibroblasts. Tenascin X modulates mechanical properties of collagen.