Repair and regeneration of the alveolar epithelium in lung injury

Considerable progress has been made in understanding the function of alveolar epithelial cells in a quiescent state and regeneration mechanism after lung injury. Lung injury occurs commonly from severe viral and bacterial infections, inhalation lung injury, and indirect injury sepsis. A series of pathological mechanisms caused by excessive injury, such as apoptosis, autophagy, senescence, and ferroptosis, have been studied. Recovery from lung injury requires the integrity of the alveolar epithelial cell barrier and the realization of gas exchange function. Regeneration mechanisms include the participation of epithelial progenitor cells and various niche cells involving several signaling pathways and proteins. While alveoli are damaged, alveolar type II (AT2) cells proliferate and differentiate into alveolar type I (AT1) cells to repair the damaged alveolar epithelial layer. Alveolar epithelial cells are surrounded by various cells, such as fibroblasts, endothelial cells, and various immune cells, which affect the proliferation and differentiation of AT2 cells through paracrine during alveolar regeneration. Besides, airway epithelial cells also contribute to the repair and regeneration process of alveolar epithelium. In this review, we mainly discuss the participation of epithelial progenitor cells and various niche cells involving several signaling pathways and transcription factors. During alveolar repair, alveolar type 2 (AT2) cell achieves self-renewal and differentiation via various transcription factors, signaling pathways, and biological processes. Besides, platelet-derived growth factor receptor alpha+ (PDGFR alpha+) lipofibroblasts, interstitial cells, macrophages, and angiocrine support the growth and differentiation of AT2 cells. HOP homeobox+ (HOPX+) alveolar type 1 (AT1) cells and airway epithelial cells have the capacity to differentiate into AT2 or AT1 cells.image