Abstract / Summary
Pulmonary fibrosis is a frequent complication of abnormal tissue repair following lung injury by many causes. It can be found in various diseases and clinical conditions, such as idiopathic pulmonary fibrosis, cancer-treatment-induced lung injury, and other occupational, environmental, and autoimmune lung diseases. Though the initiating factors of these conditions are different, they have several biological mechanisms in common during disease progression, such as injury to and abnormal repair of alveolar epithelial and vascular endothelial cells, immune microenvironment remodeling, macrophage reprogramming, persistent activation of fibroblasts, excessive extracellular matrix deposition, and mechanically driven positive feedback loops. Recent single-cell and spatial multi-omics developments have changed the direction of pulmonary fibrosis research to concentrate on individual signaling pathways to obtain a wider perspective of interactions between cell types. These investigations have discovered significant cell populations, such as abnormal basal-like epithelial cells, SPP1+/TREM2+ profibrotic macrophages, and CTHRC1+ pathological fibroblasts. They have also uncovered new processes, including metabolic–epigenetic interactions, endothelial-to-mesenchymal transition, and macrophage-to-myofibroblast transition that give a new understanding to the pathogenesis of diseases. Pirfenidone and nintedanib may slow the progression of lung dysfunction but do not reverse already existing fibrosis. Thus, knowledge of the complicated cellular and molecular processes of pulmonary fibrosis is critical in determining new therapeutic targets and enhancing existing therapies. This review summarizes pathological characteristics, mechanisms and therapeutic breakthroughs with special emphasis on idiopathic pulmonary fibrosis and cancer-therapy-related lung damage and discusses emerging strategies targeting epithelial repair, endothelial barrier activity, macrophage activity, fibroblast activation, and extracellular matrix remodeling.