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  2. 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

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

  • Toxicol Lett. 2022 Jun 15;363:45-54. doi: 10.1016/j.toxlet.2022.04.003.
Shuhong Guan 1 Hui Liu 2 Jun Zhou 3 Qiudi Zhang 1 Hui Bi 1
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, China.
  • 2 Department of Respiratory and Critical Care Medicine, the Third Clinical Medicine School of Soochow University, Changzhou, Jiangsu 213000, China.
  • 3 Department of Respiratory and Critical Care Medicine, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, China. Electronic address: [email protected].
Abstract

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.

Keywords

Pulmonary fibrosis; Tab1; Type II alveolar epithelial cell; lncRNA MIR100HG; miR-29a-3p.

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