The MIR100HG/miR-29a-3p/Tab1 axis modulates TGF-β1-induced fibrotic changes in type II alveolar epithelial cells BLM-caused lung fibrogenesis in mice

Transforming growth factor (TGF)-β1-induced fibrotic changes in alveolar epithelium is a critical event in pulmonary fibrosis. Herein, we recognized that lncRNA mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) was abnormally upregulated within human idiopathic pulmonary fibrosis (IPF) lung tissue, bleomycin (BLM)-caused pulmonary fibrotic model mice and TGF-β1-stimulated mice type II alveolar epithelial cells. In vivo, MIR100HG knockdown attenuated BLM-caused lung fibrogenesis in mice; in vitro, MIR100HG knockdown attenuated TGF-β1-induced fibrotic changes in mice type II alveolar epithelial cells. Through direct binding, MIR100HG knockdown upregulated microRNA-29a-3p (miR-29a-3p) expression; through serving as competing endogenous RNA for miR-29a-3p, MIR100HG knockdown downregulated TGF-beta activated kinase 1/MAP3K7 binding protein 1 (Tab1) expression. Finally, under TGF-β1 stimulation, Tab1 knockdown attenuated TGF-β1-induced fibrotic changes and partially attenuated the effects of miR-29a-3p inhibition. In conclusion, we demonstrated the aberrant upregulation of lncRNA MIR100HG in BLM-caused lung fibrogenesis and TGF-β1-stimulated MLE 12 cells. The MIR100HG/miR-29a-3p/Tab1 axis could modulate TGF-β1-induced fibrotic changes in type II alveolar epithelial cells and, thus, might be promising targets for pulmonary fibrosis therapy. •LncRNA MIR100HG expression is aberrantly upregulated in pulmonary fibrosis.•MIR100HG knockdown attenuates BLM-caused lung fibrogenesis in mice.•miR-29a-3p directly targets MIR100HG and Tab1.•MIR100HG/miR-29a-3p/Tab1 axis modulates TGF-β1-induced fibrotic changes in type II alveolar epithelial cells.