Fibrosis is a part of the wound-healing response to tissue damage and characterized by excessive accumulation of mainly type I collagen-containing extracellular matrices (ECMs). Transforming growth factor beta (TGF-β) is a profibrogenic master cytokine responsible for promoting differentiation of tissue-resident fibroblasts into myofibroblasts, upregulation of ECM production, and downregulation of ECM degradation. The formation of ECM is an essential response in wound healing. Fibronectin is an ECM glycoprotein substantially expressed during tissue repair. Based on in vitro findings, it has been widely accepted that collagen network organization was exclusively fibronectin matrix dependent. Unexpectedly, our fibronectin conditional knockout mouse models have demonstrated a fibronectin-independent mechanism of collagen fibril formation following injury and identified TGF-β signaling and type V collagen as essential elements for collagen fibrillogenesis. Interestingly, the targeting of the TGF-β signaling alone, as proposed in some recent antifibrotic therapies of chronic fibrotic diseases, is not sufficient to completely prevent liver fibrosis. In this chapter, we focus on the present knowledge of the mechanisms of the collagen network organization following tissue/organ damage and pathological processes of chronic fibrotic diseases.
Part of the book: Composition and Function of the Extracellular Matrix in the Human Body