Dichotomous Roles of in Macrophages and Fibroblasts in Bleomycin-Induced Pulmonary Fibrosis.

Pulmonary fibrosis therapy is limited by the unclear mechanism of its pathogenesis. C57BL/6 mice were used to construct the pulmonary fibrosis model in this study. The results showed that , which encodes menin protein, was significantly downregulated in bleomycin (BLM)-induced pulmonary fibrosis. Mice were made to overexpress or had knockdown with adeno-associated virus (AAV) infection and then induced with pulmonary fibrosis. BLM-induced pulmonary fibrosis was attenuated by overexpression and exacerbated by knockdown. Further analysis revealed the distinct roles of in fibroblasts and macrophages. inhibited fibroblast activation and extracellular matrix (ECM) protein expression while promoting macrophages to be profibrotic (M2) phenotype and enhancing their migration. Accordingly, pyroptosis was potentiated by in mouse peritoneal macrophages (PMCs) and lung tissues upon BLM stimulation. Furthermore, the expression of profibrotic factor OPN was positively regulated by menin in Raw264.7 cells and lung tissues by binding to the promoter region. Taken together, although showed antifibrotic properties in BLM-induced pulmonary fibrosis mice, conflictive roles of were displayed in fibroblasts and macrophages. The profibrotic role of in macrophages may occur via the regulation of macrophage pyroptosis and OPN expression. This study extends the current pathogenic understanding of pulmonary fibrosis.