Details

Autor(en) / Beteiligte

• Yang, Jia
• Zhou, Cheng‐Zhi
• Zhu, Rui
• Fan, Heng
• Liu, Xing‐Xing
• Duan, Xue‐Yun
• Tang, Qing
• Shou, Zhe‐Xing
• Zuo, Dong‐Mei

Titel

miR‐200b‐containing microvesicles attenuate experimental colitis associated intestinal fibrosis by inhibiting epithelial‐mesenchymal transition

Ist Teil von

• Journal of gastroenterology and hepatology, 2017-12, Vol.32 (12), p.1966-1974

Ort / Verlag

Australia: Wiley Subscription Services, Inc

Erscheinungsjahr

2017

Quelle

Wiley Online Library Journals【Remote access available】

Beschreibungen/Notizen

• Background and Aim 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.