Alveolar type 2 epithelial cell senescence and radiation-induced pulmonary fibrosis

Abstract

Radiation-induced pulmonary fibrosis (RIPF) is a chronic and progressive respiratory tract disease characterized by collagen deposition. The pathogenesis of RIPF is still unclear. Type 2 alveolar epithelial cells (AT2), the essential cells that maintain the structure and function of lung tissue, are crucial for developing pulmonary fibrosis. Recent studies indicate the critical role of AT2 cell senescence during the onset and progression of RIPF. In addition, clearance of senescent AT2 cells and treatment with senolytic drugs efficiently improve lung function and radiation-induced pulmonary fibrosis symptoms. These findings indicate that AT2 cell senescence has the potential to contribute significantly to the innovative treatment of fibrotic lung disorders. This review summarizes the current knowledge from basic and clinical research about the mechanism and functions of AT2 cell senescence in RIPF and points to the prospects for clinical treatment by targeting senescent AT2 cells.

Lipoxin A4/FPR2 signaling mitigates ferroptosis of alveolar epithelial cells via NRF2-dependent pathway during lung ischemia-reperfusion injury

“…ATII cells are one of the critical target cells for lung IRI that are involved in neutrophil chemotaxis and their dysfunction is a vital effector process of lung injury (22). In vitro studies were performed using ATII epithelial cells to investigate cell specific signaling mediated by LxA 4 in a FPR2-dependent manner ( Figure 7A ).…”

DNA‐PKcs/AKT1 inhibits epithelial–mesenchymal transition during radiation‐induced pulmonary fibrosis by inducing ubiquitination and degradation of Twist1

“…Notably, radiation can cause DNA damage, resulting in cell cycle arrest and cell senescence. Previous studies have shown that alveolar epithelial cell senescence is also a key factor in PF 41 . Furthermore, studies have suggested that DSB repair may be involved in fibrosis 42,43 .…”

“…Previous studies have shown that alveolar epithelial cell senescence is also a key factor in PF. 41 Furthermore, studies have suggested that DSB repair may be involved in fibrosis. 42,43 EMTassociated transcription factors may also regulate DSB repair, [44][45][46][47][48] indicating that there may be crosstalk between DSB repair and EMT, and the role of DNA-PKcs-mediated regulation of DSB repair and senescence in alveolar epithelial cells in RIPF needs to be further elucidated in the future.…”

Nrf-2 as a novel target in radiation induced lung injury

“…Hypoxia increases ROS production, regulates TGF-β, and promotes collagen formation, thereby reducing alveolar elasticity [ 20 ]. In addition, ROS can cause cell loss, alveolar wall edema, increased vascular permeability, and protein exudation, further reducing lung elasticity, destroying vascular integrity, and increasing the apoptosis of alveolar type I epithelial cells, thereby promoting alveolar type II epithelial cell proliferation and aggravating lung inflammation [ 10 , 21 ]. Under long-term cytokine action, fibroblast recruitment and myofibroblast proliferation lead to the remodeling of the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT), resulting in fibrogenesis and scar formation, eventually replacing the normal lung tissue with the development of advanced PF [ 22 , 23 ].…”