fibrogenesis

Fibrogenesis is the biological process by which fibrous connective tissue is formed as part of wound healing and, in some settings, as a feature of chronic disease. It involves activation and differentiation of mesenchymal cells into myofibroblasts that synthesize and remodel extracellular matrix (ECM), especially fibrillar collagens such as types I and III, fibronectin, and proteoglycans. In normal repair, fibrogenesis is tightly regulated and limited in duration; in chronic injury, it becomes persistent, leading to excessive ECM deposition, tissue stiffness, and architectural disruption.

Molecular and cellular drivers include injury-induced inflammatory signals, with transforming growth factor-beta (TGF-β) cited as a central profibrotic cytokine that promotes myofibroblast formation and collagen production. Other mediators, such as PDGF and CTGF, support fibroblast proliferation and matrix deposition. Matrix turnover is governed by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs); a tilt toward TIMPs and cross-linking enzymes like lysyl oxidase favors matrix accumulation and stiffness.

Cellular sources of ECM-producing cells include resident fibroblasts, pericytes, and, in certain organs, activated stellate cells (notably in the liver). While myofibroblasts are key effectors, processes such as epithelial-to-mesenchymal transition and endothelial-to-mesenchymal transition have been described in some settings, though their contributions vary.

Organ-specific contexts often cited include hepatic fibrogenesis driven by stellate cell activation and pulmonary fibrogenesis resulting from alveolar injury. Clinically, progressive fibrogenesis can lead to irreversible scarring and organ dysfunction, though in some cases removal of the injurious stimulus allows partial or complete reversal through ECM remodeling. Antifibrotic strategies aim to interrupt profibrotic signaling, with TGF-β pathways among common targets.