Fig. 3 |. Key mechanisms involved in the development of pulmonary fibrosis.

a, Premature senescence of the type 2 alveolar epithelial cell. This is driven by a combination of genetic polymorphisms, environmental exposure (inhaled dust, viruses and cigarette smoke) and/or autoimmune disease that results in cell injury and ageing with telomere shortening and attrition. b, This premature senescence of type 2 cells results in a failure of re-epithelialization of the basement membrane following subsequent injury. This in turn leads to activation of fibroblasts with transformation into myofibroblasts, which then produce collagen and extracellular matrix. Endothelial cell activation results in vascular leak and activation of platelets, fibrin and other components of the clotting cascade. Resident alveolar macrophages and circulating monocytes contribute to the profibrotic milieu by producing profibrotic growth factors. These changes lead to impaired gas transfer and ultimately to respiratory failure. MUC5B, mucin 5B; RBC, red blood cell.