PMID- 33482190 OWN - NLM STAT- MEDLINE DCOM- 20210226 LR - 20210226 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 269 DP - 2021 Mar 15 TI - The MIR155 host gene/microRNA-627/HMGB1/NF-kappaB loop modulates fibroblast proliferation and extracellular matrix deposition. PG - 119085 LID - S0024-3205(21)00070-9 [pii] LID - 10.1016/j.lfs.2021.119085 [doi] AB - Pulmonary fibrosis (PF), which is characterized by excessive matrix formation, may ultimately lead to irreversible lung damage and thus death. Fibroblast activation has been regarded as a central event during PF pathogenesis. In our previous study, we confirmed that the miR-627/high-mobility group box protein 1 (HMGB1)/Nuclear factor kappa beta (NF-kappaB) axis modulates transforming growth factor beta 1 (TGFbeta1)-induced pulmonary fibrosis. In the present study, we investigated the upstream factors leading to miR-627 dysregulation in the process of pulmonary fibroblast activation and PF. The lncRNA MIR155 host gene (MIR155HG) was found to be abnormally upregulated in pulmonary fibrosis tissues and TGFbeta1-stimulated normal human primary lung fibroblasts (NHLFs). By directly binding to miR-627, MIR155HG inhibited miR-627 expression. MIR155HG overexpression enhanced TGFbeta1-induced increases in HMGB1 protein expression and p65 phosphorylation, NHLF proliferation, and extracellular matrix (ECM) deposition. In contrast, miR-627 overexpression attenuated the TGFbeta1-induced changes in NHLFs and significantly reversed the effects of MIR155HG overexpression. Under TGFbeta1 stimulation, miR-627 inhibition promoted, whereas JSH-23 treatment inhibited NF-kappaB activation; in NHLFs, NF-kappaB overexpression upregulated, whereas JSH-23 treatment downregulated MIR155HG expression. In tissue samples, HMGB1 protein levels and p65 phosphorylation were increased; MIR155HG was negatively correlated with miR-627 and positively correlated with HMGB1. In conclusion, we validated that the MIR155HG/miR-627/HMGB1/NF-kappaB axis formed a regulatory loop that modulates TGFbeta1-induced NHLF activation. Considering the critical role of NHLF activation in PF pathogenesis, the NF-kappaB/MIR155HG/miR-627/HMGB1 regulatory loop could exert a vital effect on PF pathogenesis. Further in vivo and clinical investigations are required to confirm this model. CI - Copyright (c) 2021. Published by Elsevier Inc. FAU - Li, Jie AU - Li J AD - Department of Internal Medicine, Jiangxi Chest Hospital, Nanchang 330006, China. FAU - Zhang, Xueyu AU - Zhang X AD - Department of Internal Medicine, Jiangxi Chest Hospital, Nanchang 330006, China. FAU - Wang, Tao AU - Wang T AD - Department of Thoracic Surgery, Jiangxi Chest Hospital, Nanchang 330006, China. FAU - Li, Jinghong AU - Li J AD - Department of Internal Medicine, Jiangxi Chest Hospital, Nanchang 330006, China. FAU - Su, Qi AU - Su Q AD - Medical Department, Jiangxi Chest Hospital, Nanchang 330006, China. FAU - Zhong, Cheng AU - Zhong C AD - Department of Internal Medicine, Jiangxi Chest Hospital, Nanchang 330006, China. FAU - Chen, Zhongshu AU - Chen Z AD - Department of Thoracic Surgery, Jiangxi Chest Hospital, Nanchang 330006, China. Electronic address: czs680819@126.com. FAU - Liang, Ying AU - Liang Y AD - Department of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China. Electronic address: Liangying498@163.com. LA - eng PT - Journal Article DEP - 20210120 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, human) RN - 0 (MIRN155 microRNA, human) RN - 0 (MIRN627 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NF-kappa B) RN - 0 (RNA, Long Noncoding) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Case-Control Studies MH - Cell Proliferation MH - Extracellular Matrix/*metabolism MH - Fibroblasts/*cytology/metabolism MH - Gene Expression Regulation MH - HMGB1 Protein/genetics/*metabolism MH - Humans MH - Lung/cytology/metabolism MH - MicroRNAs/*genetics MH - NF-kappa B/genetics/*metabolism MH - Pulmonary Fibrosis/genetics/metabolism/*pathology MH - RNA, Long Noncoding/*genetics MH - Signal Transduction MH - Transforming Growth Factor beta1/genetics/metabolism OTO - NOTNLM OT - Fibroblast activation OT - High-mobility group box protein 1 (HMGB1) OT - MIR155 host gene (MIR155HG) OT - Nuclear factor kappa beta (NF-kappaB) OT - Pulmonary fibrosis (PF) OT - miR-627 EDAT- 2021/01/23 06:00 MHDA- 2021/02/27 06:00 CRDT- 2021/01/22 20:09 PHST- 2020/10/30 00:00 [received] PHST- 2021/01/08 00:00 [revised] PHST- 2021/01/12 00:00 [accepted] PHST- 2021/01/23 06:00 [pubmed] PHST- 2021/02/27 06:00 [medline] PHST- 2021/01/22 20:09 [entrez] AID - S0024-3205(21)00070-9 [pii] AID - 10.1016/j.lfs.2021.119085 [doi] PST - ppublish SO - Life Sci. 2021 Mar 15;269:119085. doi: 10.1016/j.lfs.2021.119085. Epub 2021 Jan 20.