Zinc Restrains Multicellular Remodeling in Fibrotic Lung Disease

Rather than acting on a single effector, high-zinc diet broadly restrained disease-associated multicellular remodeling, including SPP1+ IM expansion, myofibroblast activation, transitional AT1/2 epithelial cell accumulation, and pro-fibrotic gene upregulation. Notably, the zinc-responsive transcriptional changes converged with pathways activated in human IPF, highlighting the translational relevance of our findings.

In contrast, low-zinc diet exacerbated these pathological changes, underscoring the sensitivity of lung fibrotic remodeling to zinc availability. These results extend prior work linking zinc transporter ZIP8 to alveolar progenitor renewal and place zinc biology within a broader multicellular network of IPF pathogenesis. The precise mechanisms by which zinc restrains multicellular remodeling and whether zinc supplementation benefits established fibrosis remain important questions for future investigation.