PMID- 30463065 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20211102 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 51 IP - 2 DP - 2018 TI - MicroRNA-485 Modulates the TGF-beta/ Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2. PG - 692-710 LID - 10.1159/000495327 [doi] AB - BACKGROUND/AIMS: Chronic respiratory conditions continue to plague millions of people worldwide. We aimed to elucidate the detailed mechanisms of microRNA-485 (miR-485) in airway smooth muscle cell (ASMC) proliferation and apoptosis in chronic asthmatic mice. METHODS: A mouse model of chronic asthma was established. Ovalbumin was used to induce chronic asthma in the mice. The levels of transforming growth factor beta (TGF-beta), interleukin (IL)-4, IL-5, IL-13 and IL-17 in bronchoalveolar lavage fluid in mice were measured by enzyme-linked immunoassays (ELISAs). ASMCs were transfected with miR-485 mimic, miR-485 inhibitor and siRNA-Smurf2. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were applied to detect the mRNA and protein levels of Smurf2, alpha-SMA, TGF-beta1 and decapentaplegic homolog (Smads). The MTT assay was utilized for cell proliferation, while flow cytometry was conducted to assess cell cycle distribution and apoptosis. RESULTS: Lower expression of miR-485 and higher expression levels of TGF-beta1, IL-4, IL-5, IL-13 and IL-17 were detected in mice with chronic asthma. Smurf2 was identified as the target gene of miR-485. Upregulation of miR-485 mimic and downregulation of Smurf2 decreased expression levels of Smurf2, alpha-SMA, TGF-beta1 and Smad3, inhibited cell proliferation and increased apoptosis, while contrary results were observed in ASMCs transfected with miR-485 inhibitor. CONCLUSION: Overexpressed miR-485 inhibits cell proliferation and promotes apoptosis of ASMCs through the Smurf2-mediated TGF-beta/Smads signaling pathway in mice with chronic asthma. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - Wang, Jing AU - Wang J AD - Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun, China. FAU - Li, Hong-Yan AU - Li HY AD - Department of Infections, China-Japan Union Hospital of Jilin University, Changchun, China. FAU - Wang, Hu-Shan AU - Wang HS AD - Department of Anesthesiology, The First Hospital of Jilin University, Changchun, China. FAU - Su, Zhen-Bo AU - Su ZB AD - Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Chinasuzb@jlu.edu.cn. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20181121 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (3' Untranslated Regions) RN - 0 (Antagomirs) RN - 0 (Cytokines) RN - 0 (MicroRNAs) RN - 0 (RNA, Small Interfering) RN - 0 (Smad Proteins) RN - 0 (Transforming Growth Factor beta) RN - EC 2.3.2.26 (Smurf2 protein, mouse) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM RIN - Cell Physiol Biochem. 2021;55(5):658. PMID: 34727432 MH - 3' Untranslated Regions MH - Animals MH - Antagomirs/metabolism MH - Apoptosis MH - Asthma/metabolism/pathology/veterinary MH - Cell Proliferation MH - Chronic Disease MH - Cytokines/metabolism MH - Female MH - G1 Phase Cell Cycle Checkpoints MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/antagonists & inhibitors/genetics/*metabolism MH - Myocytes, Smooth Muscle/cytology/metabolism MH - RNA Interference MH - RNA, Small Interfering/metabolism MH - Signal Transduction MH - Smad Proteins/metabolism MH - Transforming Growth Factor beta/metabolism MH - Ubiquitin-Protein Ligases/antagonists & inhibitors/genetics/*metabolism OTO - NOTNLM OT - Apoptosis OT - Chronic asthma OT - MicroRNA-485 OT - Proliferation OT - Smurf2 OT - TGF-beta/Smads signaling pathway EDAT- 2018/11/22 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/11/22 06:00 PHST- 2017/12/14 00:00 [received] PHST- 2018/11/13 00:00 [accepted] PHST- 2018/11/22 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/11/22 06:00 [entrez] AID - 000495327 [pii] AID - 10.1159/000495327 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;51(2):692-710. doi: 10.1159/000495327. Epub 2018 Nov 21.