Collagen in Fibrotic Diseases

This chapter explores the role of fibrillar collagens, mainly collagen I, in developing fibrotic disorders associated with acute or chronic injuries. While collagen molecules' fundamental structure, composition, and intracellular biosynthesis steps remain similar in healthy and scar tissues, their extracellular architecture and physical properties significantly differ. These differences arise from the excessive production of collagen I and auxiliary proteins associated with collagen I folding and posttranslational modifications. As a result, the overaccumulation of collagen I-based fibrotic deposits creates a rigid mechanical environment that, through mechanotransduction, amplifies pro-fibrotic signaling in resident fibroblasts.In reviewing the literature, this chapter highlights key players that create, transmit, and sustain these signals, thereby perpetuating fibrosis. Given the growing recognition of mechanotransduction as a valid therapeutic target to limit fibrosis, this chapter also discusses strategies to inhibit different elements of this process. A significant challenge with these strategies is that both balanced and excessive scarring rely on the exact underlying mechanisms of scar tissue formation. Consequently, conventional anti-fibrotic agents may inadvertently impair the essential scarring needed to preserve tissue integrity after injury. Therefore, mechanotherapeutics that reduce collagen accumulation-driven scar stiffness represent a novel approach for developing more targeted anti-fibrotic therapies.