Mechanism of fibrosis

Fibrosis is characterized by replacement of normal tissue architecture with stiff collagen-rich connective tissue. Fibrosis is the hallmark of scleroderma, as well as a large and heterogeneous group of human diseases. In these conditions, fibrosis represents the end result of a complex series of vascular and immune-mediated responses to injury in a genetically predisposed individual [1]. As illustrated in Fig. 21.1, injured or activated vascular, epithelial and immune cells produce soluble mediators, autoantibodies and reactive oxygen species (ROS) that induce the activation and differentiation of mesenchymal cells, leading to excessive matrix deposition and increasing stiffness and ultimately irreversible remodeling, and fibrosis.