目的 Idiopathic pulmonary fibrosis (IPF) is a severe health problem worldwide and has one of the poorest prognoses.C/EBP homologous protein (Chop), one of the endoplasmic reticulum (ER) stress markers, has been found with altered expression in patients with IPF, while its exact role in IPF pathoetiology is yet to be fully addressed.方法 Studies were conducted in IPF patients and Chop-/- mice to dissect the role of Chop and ER stress in pulmonary fibrosis pathogenesis.Bleomycin (BLM) was employed to induce mice with onset of pulmonary fibrosis to address the impact of Chop deficiency on the development of pulmonary fibrosis.The effect of Chop deficiency on macrophage polarization and related signaling pathways were next investigated to demonstrate the underlying mechanisms.结果 IPF patients and mice with onset BLM-induced pulmonary fibrosis experienced altered Chop expression and ER stress.In particular, Chop was predominantly overexpressed by the infiltrated macrophages.As a result, the loss of Chop protected mice against BLM-induced pulmonary fibrosis.Mice deficient in Chop were characterized by a reduced TGF-β production along with attenuated Smda2/3 signalling following BLM induction.Mechanistic studies showed that Chop deficiency enhanced the expression of SOCS1 and 3 and then repressed the activity of STAT6/PPAR-γ signalling to attenuate the M2 program in macrophages.Thereafter, the loss of Chop reduced the production of TGF-β.As a result, WT and Chop-/- mice manifested with a similar disease severity following BLM induction once macrophages were depleted or WT M2 macrophages were adoptively transferred into the lungs after depletion of endogenous macrophages.结论 These results not only provided novel insights into the understanding of IPF pathoaetiology but also provided evidence supporting that targeting Chop-related ER stress could be a viable strategy for the prevention and treatment of pulmonary fibrosis in clinical settings.