PMID- 35472619 OWN - NLM STAT- MEDLINE DCOM- 20220613 LR - 20220614 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 363 DP - 2022 Jun 15 TI - The MIR100HG/miR-29a-3p/Tab1 axis modulates TGF-beta1-induced fibrotic changes in type II alveolar epithelial cells BLM-caused lung fibrogenesis in mice. PG - 45-54 LID - S0378-4274(22)00086-8 [pii] LID - 10.1016/j.toxlet.2022.04.003 [doi] AB - Transforming growth factor (TGF)-beta1-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-beta1-stimulated mice type II alveolar epithelial cells. In vivo, MIR100HG knockdown attenuated BLM-caused lung fibrogenesis in mice; in vitro, MIR100HG knockdown attenuated TGF-beta1-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-beta1 stimulation, Tab1 knockdown attenuated TGF-beta1-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-beta1-stimulated MLE 12 cells. The MIR100HG/miR-29a-3p/Tab1 axis could modulate TGF-beta1-induced fibrotic changes in type II alveolar epithelial cells and, thus, might be promising targets for pulmonary fibrosis therapy. CI - Copyright (c) 2022. Published by Elsevier B.V. FAU - Guan, Shuhong AU - Guan S AD - Department of Respiratory and Critical Care Medicine, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, China. FAU - Liu, Hui AU - Liu H AD - Department of Respiratory and Critical Care Medicine, the Third Clinical Medicine School of Soochow University, Changzhou, Jiangsu 213000, China. FAU - Zhou, Jun AU - Zhou J AD - Department of Respiratory and Critical Care Medicine, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, China. Electronic address: zsj67720@czfph.com. FAU - Zhang, Qiudi AU - Zhang Q AD - Department of Respiratory and Critical Care Medicine, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, China. FAU - Bi, Hui AU - Bi H AD - Department of Respiratory and Critical Care Medicine, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, China. LA - eng PT - Journal Article DEP - 20220423 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (MicroRNAs) RN - 0 (Mirn100 microRNA, mouse) RN - 0 (RNA, Long Noncoding) RN - 0 (Tab1 protein, mouse) RN - 0 (Transforming Growth Factor beta1) RN - 11056-06-7 (Bleomycin) SB - IM MH - Adaptor Proteins, Signal Transducing/metabolism MH - Alveolar Epithelial Cells/metabolism MH - Animals MH - Bleomycin/toxicity MH - Epithelial-Mesenchymal Transition MH - Fibrosis MH - *Idiopathic Pulmonary Fibrosis/chemically induced/genetics/metabolism MH - Lung MH - Mice MH - *MicroRNAs/metabolism MH - *RNA, Long Noncoding/genetics/metabolism MH - Transforming Growth Factor beta1/metabolism OTO - NOTNLM OT - Pulmonary fibrosis OT - Tab1 OT - Type II alveolar epithelial cell OT - lncRNA MIR100HG OT - miR-29a-3p EDAT- 2022/04/27 06:00 MHDA- 2022/06/14 06:00 CRDT- 2022/04/26 20:10 PHST- 2021/09/10 00:00 [received] PHST- 2022/02/14 00:00 [revised] PHST- 2022/04/20 00:00 [accepted] PHST- 2022/04/27 06:00 [pubmed] PHST- 2022/06/14 06:00 [medline] PHST- 2022/04/26 20:10 [entrez] AID - S0378-4274(22)00086-8 [pii] AID - 10.1016/j.toxlet.2022.04.003 [doi] PST - ppublish SO - Toxicol Lett. 2022 Jun 15;363:45-54. doi: 10.1016/j.toxlet.2022.04.003. Epub 2022 Apr 23.