Beryllium Sulfate–Induced Cellular Senescence via the IL‐6/STAT3 Pathway to Promote Pulmonary Fibrosis

ABSTRACT Beryllium is widely used in nuclear technology, aerospace, and defense. Long‐term beryllium exposure causes chronic beryllium disease (CBD) characterized predominantly by pulmonary fibrosis. Cellular senescence is an important mechanism underlying pulmonary fibrosis, and the IL‐6/STAT3 pathway has been implicated as a central axis linking inflammation, senescence, and tissue remodeling. However, whether this pathway promotes beryllium sulfate (BeSO 4 )–induced pulmonary fibrosis through regulation of senescence remains unclear. Herein, Sprague–Dawley rats were exposed to BeSO 4 , and hematoxylin–eosin (H&E) and Masson's trichrome staining were used to assess lung injury and fibrosis. Immunohistochemistry (IHC) assays were used to assess fibrosis‐related factors, pathway molecules, and senescence markers in the lung tissues. In vitro, A549 cells were pretreated with the IL‐6/STAT3 inhibitor LMT‐28 before BeSO 4 exposure, and alterations in cell morphology, proliferation, senescence‐related markers, and fibrosis‐related markers were evaluated. The results demonstrated that BeSO 4 exposure promoted cellular senescence and pulmonary fibrogenesis via activating IL‐6/STAT3 signaling, whereas LMT‐28 treatment significantly attenuated these processes. These findings elucidate the molecular mechanism by which BeSO 4 induces pulmonary fibrosis through cellular aging, providing a basis for the discovery of potential therapeutic targets.