Autophagy-epithelial-mesenchymal transition crosstalk in acute respiratory distress syndrome: Mechanistic insights and therapeutic perspectives (Review).

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary disorder frequently encountered in intensive care units, characterized by diffuse alveolar damage, intense inflammatory infiltration and progressive fibrotic remodeling. Among the mechanisms driving fibrosis, the epithelial-mesenchymal transition (EMT) has gained increasing recognition as a key contributor to the generation of fibroblasts and extracellular matrix deposition. Autophagy, a tightly regulated intracellular degradation and recycling process, serves a context-dependent role in EMT regulation and lung injury. While basal autophagy supports pulmonary cellular homeostasis, dysregulated or excessive autophagy may exacerbate tissue injury and maladaptive repair. The literature has previously highlighted both classical macroautophagy and selective autophagy pathways, including mitophagy, endoplasmic reticulum-selective autophagy and ferritinophagy, as modulators of EMT dynamics and fibrotic outcomes. However, the mechanistic associations between specific autophagy subtypes and EMT in ARDS remain poorly defined and occasionally contradictory. In the present review, current evidence on autophagy-EMT crosstalk in ARDS is critically appraised, conceptual gaps and controversies are identified and further potential mechanistic frameworks and research priorities are summarized. Such investigation may help inform the rational targeting of autophagy pathways in future ARDS therapies.