PMID- 32898329 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211211 IS - 2001-1326 (Print) IS - 2001-1326 (Electronic) IS - 2001-1326 (Linking) VI - 10 IP - 4 DP - 2020 Aug TI - Mir-27a-3p attenuates bronchiolitis obliterans in vivo via the regulation of dendritic cells' maturation and the suppression of myofibroblasts' differentiation. PG - e140 LID - 10.1002/ctm2.140 [doi] LID - e140 AB - Bronchiolitis obliterans (BO), is a chronic rejection phenotype characterized by chronic small airway fibrous obliteration, hinders the patients who suffer from lung transplanting for surviving longer. Cell-based therapies using dendritic cells (DCs) and T regulatory cells (Tregs) have been developed to regulate allograft rejection, and to induce and maintain immune tolerance. In the present study, the effects of mir-27a-3p on regulating DCs as well as resulting effects on BO attenuation have been investigated. According to our reporter assays, the potential targets of mir-27a-3p were Smad2, sprouty2, and Smad4, respectively. Furthermore, sprouty2 inhibition by mir-27-3p indirectly activated extracellular regulated protein kinases (ERK) and increased IL-10 production in DCs. This led to a positive feedback loop that maintained the immature state of DCs via IL-10/JAK/STAT3 pathway, and caused an increase in Foxp3(+) CD4(+) T cells amount as well as TGF-beta level. Furthermore, mir-27a-3p regulated TGF-beta function, inhibited TGF-beta/Smad pathway, and suppressed myofibroblast differentiation through influencing the function of Smad2 and Smad4. In short, the study indicated the effect of mir-27a-3p on suppressing DC maturation, which implicated the potential clinical application in treating postlung transplant BO. CI - (c) 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. FAU - Dong, Ming AU - Dong M AUID- ORCID: 0000-0002-0296-3519 AD - Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, P. R. China. FAU - Wang, Xin AU - Wang X AD - Department of Pediatric Surgery, Tianjin Children's Hospital, Tianjin, P. R. China. FAU - L, Tong AU - L T AD - Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, P. R. China. FAU - Wang, Jing AU - Wang J AD - Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, P. R. China. FAU - Yang, Yunwei AU - Yang Y AD - School of Basic Medical Sciences, Tianjin Medical University, Tianjin, P. R. China. FAU - Liu, Yi AU - Liu Y AD - School of Basic Medical Sciences, Tianjin Medical University, Tianjin, P. R. China. FAU - Jing, Yaqing AU - Jing Y AD - School of Basic Medical Sciences, Tianjin Medical University, Tianjin, P. R. China. FAU - Zhao, Honglin AU - Zhao H AD - Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, P. R. China. FAU - Chen, Jun AU - Chen J AD - Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, P. R. China. LA - eng GR - 18JCYBJC92600/Natural Science Foundation of Tianjin City/ GR - 81600073/National Natural Science Foundation of China/ GR - 320.6750.18157/Wu Jieping Medical Foundation/ GR - HZB-20181119-7/Bethune Ethicon Excellent Surgery Foundation/ PT - Journal Article PL - United States TA - Clin Transl Med JT - Clinical and translational medicine JID - 101597971 EIN - Clin Transl Med. 2021 Jun;11(6):e433. PMID: 34185434 PMC - PMC7423186 OTO - NOTNLM OT - bronchiolitis obliterans OT - dendritic cells OT - lung transplantation OT - mir-27a-3p COIS- The authors declare that they have no conflict of interest. EDAT- 2020/09/09 06:00 MHDA- 2020/09/09 06:01 PMCR- 2020/08/12 CRDT- 2020/09/08 17:13 PHST- 2020/05/05 00:00 [received] PHST- 2020/07/16 00:00 [revised] PHST- 2020/07/17 00:00 [accepted] PHST- 2020/09/08 17:13 [entrez] PHST- 2020/09/09 06:00 [pubmed] PHST- 2020/09/09 06:01 [medline] PHST- 2020/08/12 00:00 [pmc-release] AID - CTM2140 [pii] AID - 10.1002/ctm2.140 [doi] PST - ppublish SO - Clin Transl Med. 2020 Aug;10(4):e140. doi: 10.1002/ctm2.140.