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

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.