Pulmonary fibrosis (PF) is a group of chronic progressive lung diseases characterized by irreversible remodeling of lung tissue structure, abnormal proliferation of fibroblasts, and excessive deposition of extracellular matrix (ECM), among which idiopathic pulmonary fibrosis (IPF) is the most typical subtype. Currently, the only two clinically approved therapeutic drugs (nintedanib and pirfenidone) can only partially slow disease progression without reversing fibrotic lesions, and are associated with varying degrees of adverse effects. Oxidative stress, defined as a pathological imbalance between systemic oxidant and antioxidant systems, has been substantiated by extensive research as a pivotal mechanism driving the pathogenesis and progression of pulmonary fibrosis. This review summarizes the regulatory mechanisms of oxidative stress in pulmonary fibrosis, with a focus on its critical role in inducing and promoting fibrosis through relevant target cells and signaling pathways. We also specifically highlight the latest progress and challenges in therapeutic strategies targeting oxidative stress, and discuss next-generation therapies, including the modulation of endogenous antioxidant pathways, supplementation of exogenous antioxidants, as well as nanomaterials, exosomes, and combination therapies. We hope this review will deepen the understanding of oxidative stress and pulmonary fibrosis, and provide new directions for improving the clinical efficacy of oxidative stress-targeted therapies.
Xu et al. (Thu,) studied this question.