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.

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.
Authors	Shuhong Guan, Hui Liu, Jun Zhou, Qiudi Zhang, Hui Bi
Journal	Toxicology letters (Toxicol Lett) Vol. 363 Pg. 45-54 (Jun 15 2022) ISSN: 1879-3169 [Electronic] Netherlands
PMID	35472619 (Publication Type: Journal Article)
Copyright	Copyright © 2022. Published by Elsevier B.V.
Chemical References	Adaptor Proteins, Signal Transducing MicroRNAs Mirn100 microRNA, mouse RNA, Long Noncoding Tab1 protein, mouse Transforming Growth Factor beta1 Bleomycin
Topics	Adaptor Proteins, Signal Transducing (metabolism) Alveolar Epithelial Cells (metabolism) Animals Bleomycin (toxicity) Epithelial-Mesenchymal Transition Fibrosis Idiopathic Pulmonary Fibrosis (chemically induced, genetics, metabolism) Lung Mice MicroRNAs (metabolism) RNA, Long Noncoding (genetics, metabolism) Transforming Growth Factor beta1 (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!