PMID- 33089914 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20221005 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 24 IP - 23 DP - 2020 Dec TI - Phosphorylated STAT3 suppresses microRNA-19b/1281 to aggravate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis. PG - 13763-13774 LID - 10.1111/jcmm.15954 [doi] AB - Type 2 diabetes mellitus (T2DM) is a risk factor for pulmonary tuberculosis (PTB) and increased mortality. This work focused on the functions of phosphorylated STAT3 in lung injury in mouse with T2DM-associated PTB and the molecules involved. A mouse model with T2DM-PTB was induced by administrations of streptozotocin, nicotinamide and mycobacterium tuberculosis (Mtb). A pSTAT3-specific inhibitor AG-490 was given into mice and then the lung injury in mice was observed. The molecules involved in AG-490-mediated events were screened out. Altered expression of miR-19b, miR-1281 and NFAT5 was introduced to identify their involvements and roles in lung injury and PTB severity in the mouse model. Consequently, pSTAT3 expression in mice with T2DM-associated PTB was increased. Down-regulation of pSTAT3 by AG-490 prolonged the lifetime of mice and improved the histopathologic conditions, and inhibited the fibrosis, inflammation, Mtb content and number of apoptotic epithelial cells in mouse lung tissues. pSTAT3 transcriptionally suppressed miR-19b/1281 expression to up-regulate NFAT5. Inhibition of miR-19b/1281 or up-regulation of NFAT5 blocked the protective roles of AG-490 in mouse lung tissues. To conclude, this study evidenced that pSTAT3 promotes NFAT5 expression by suppressing miR-19b/1281 transcription, leading to lung injury aggravation and severity in mice with T2DM-associated PTB. CI - (c) 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Wang, Xianhua AU - Wang X AUID- ORCID: 0000-0003-4155-7924 AD - Department of Quality Control, Center for Disease Control and Prevention of Changji Hui Autonomous Prefecture, Changji, China. FAU - Lin, Yuefu AU - Lin Y AD - Department of Prevention, Linyi People's Hospital, Linyi, China. FAU - Liang, Ying AU - Liang Y AD - Department of Nutrition and Food Hygiene, School of Public Health, Xinjiang Medical University, Urumqi, China. FAU - Ye, Yang AU - Ye Y AD - Department of Laboratory, People's Hospital of Changji Hui Autonomous Prefecture, Changji, China. FAU - Wang, Dong AU - Wang D AD - Department of Tuberculosis, Center for Disease Control and Prevention of Changji Hui Autonomous Prefecture, Changji, China. FAU - Tai, Aer AU - Tai A AD - Department of Respiratory Medicine, Xinjiang Uygur Autonomous Region Chest Hospital, Urumqi, China. FAU - Wu, Shuimiao AU - Wu S AD - Department of Respiratory and Critical Care Medicine, Weinan Central Hospital, Weinan, China. FAU - Pan, Jian AU - Pan J AD - Department of Respiratory and Critical Care Medicine, The Third People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201022 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Biomarkers) RN - 0 (MIRN19 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (STAT3 Transcription Factor) SB - IM MH - Animals MH - Apoptosis/genetics MH - Biomarkers MH - Biopsy MH - Diabetes Mellitus, Type 2/*complications MH - Disease Models, Animal MH - Disease Susceptibility MH - *Gene Expression Regulation MH - Genes, Reporter MH - Immunohistochemistry MH - Mice MH - MicroRNAs/*genetics MH - Phosphorylation MH - STAT3 Transcription Factor/*metabolism MH - Tuberculosis, Pulmonary/*etiology/*metabolism/pathology PMC - PMC7754065 OTO - NOTNLM OT - NAFT5 OT - Type 2 diabetes mellitus OT - inflammation OT - microRNA-1281 OT - microRNA-19b OT - phosphorylated STAT3 OT - pulmonary tuberculosis COIS- The authors declare no potential conflicts of interest. EDAT- 2020/10/23 06:00 MHDA- 2021/05/15 06:00 PMCR- 2020/12/01 CRDT- 2020/10/22 08:49 PHST- 2020/05/14 00:00 [received] PHST- 2020/08/09 00:00 [revised] PHST- 2020/08/19 00:00 [accepted] PHST- 2020/10/23 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/10/22 08:49 [entrez] PHST- 2020/12/01 00:00 [pmc-release] AID - JCMM15954 [pii] AID - 10.1111/jcmm.15954 [doi] PST - ppublish SO - J Cell Mol Med. 2020 Dec;24(23):13763-13774. doi: 10.1111/jcmm.15954. Epub 2020 Oct 22.