title: miR-200b-containing microvesicles attenuate experimental colitis associated intestinal fibrosis by inhibiting epithelial-mesenchymal transition.
abstract: OBJECTIVE
  Epithelial-mesenchymal transition (EMT), characterized by the decrease of E-cadherin (E-Cad) and increase in vimentin and alpha-smooth muscle actin (α-SMA), was demonstrated to participate in inflammatory bowel disease-related fibrosis. miR-200b plays an anti-fibrosis role in inhibiting EMT by targeting ZEB1 and ZEB2. But the stability of exogenous miR-200b in blood limits its application. Microvesicles (MVs), which can transfer miRNAs among cells and prevent them from degradation, may provide an excellent transport system for the delivery of miR-200b in the treatment of fibrosis.
  
  
  METHODS
  Bone marrow mesenchymal stem cells (BMSCs) were transfected with lentivirus to overexpress miR-200b. The MVs packaged with miRNA-200b were harvested for the anti-fibrotic treatment using in vitro (transforming growth factor beta 1-mediated EMT in intestinal epithelial cells: IEC-6) and in vivo (TNBS-induced intestinal fibrosis in rats) models. The pathological morphology was observed, and the fibrosis related proteins, such as E-Cad, vimentin, α-SMA, ZEB1, and ZEB2, were detected.
  
  
  RESULTS
  MiR-200b-MVs would significantly reverse the morphology in TGF-β1-treated IEC-6 cells and improve the TNBS-induced colon fibrosis histologically. The treatment of miR-200b-MVs increased miR-200b levels both in the IEC-6 cells and colon, resulting in a significant prevention EMT and alleviation of fibrosis. The expression of E-Cad was increased, and the expressions of vimentin and α-SMA were decreased. ZBE1 and ZEB2, the targets of miR-200b, were also decreased.
  
  
  CONCLUSIONS
  miR-200b could be transferred from genetically modified BMSCs to the target cells or tissue by MVs. The mechanisms of miR-200b-MVs in inhibiting colonic fibrosis were related to suppressing the development of EMT by targeting ZEB1and ZEB2.
authors.affiliation: Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Department of Cardiology, The Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, China.
authors.forename: Cheng-Zhi
authors.initials: CZ
authors.lastname: Zhou
authors.affiliation: Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, The Affiliated Hospital of Hubei University of Traditional Chinese Medicine, Wuhan, China.
authors.forename: Xue-Yun
authors.initials: XY
authors.lastname: Duan
authors.affiliation: Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhe-Xing
authors.initials: ZX
authors.lastname: Shou
authors.affiliation: Department of Integrated Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zuo
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D055252:Cell-Derived Microparticles; D002478:Cells, Cultured; D003092:Colitis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005355:Fibrosis; D018398:Homeodomain Proteins; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D058990:Molecular Targeted Therapy; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors; D014746:Vimentin / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D000199:Actins; D015820:Cadherins; D018398:Homeodomain Proteins; D035683:MicroRNAs; D014157:Transcription Factors; D014746:Vimentin; D000071799:Zinc Finger E-box-Binding Homeobox 1; C555600:MIRN200 microRNA, rat; C000630720:ZEB1 protein, rat; C498862:Acta2 protein, rat
keywords: epithelial-mesenchymal transition; intestinal fibrosis; miR-200b; microvesicles