PMID- 28963073 OWN - NLM STAT- MEDLINE DCOM- 20180206 LR - 20181202 IS - 1879-0542 (Electronic) IS - 0165-2478 (Linking) VI - 191 DP - 2017 Nov TI - BM-MSCs-derived microvesicles promote allogeneic kidney graft survival through enhancing micro-146a expression of dendritic cells. PG - 55-62 LID - S0165-2478(17)30060-3 [pii] LID - 10.1016/j.imlet.2017.09.010 [doi] AB - OBJECTIVE: Microvesicles (MVs) are plasmalemmal vesicles that are released from various cells and regarded as a mediator of intermolecular communication. In present study, we aimed to evaluate the therapeutic efficacy of the bone marrow mesenchymal stem cells (BM-MSCs)-derived MVs in the mice kidney transplant model and explored the underlying mechanism. METHODS: BM-MSCs were isolated from C57BL/6 mice and identified using flow cytometry. In vivo allogenic kidney transplantation model of mice was performed between C57BL/6 mice (recipient) and BALB/c mice (donor). Recipient-type BM-MSC (0.1ml) or equal volume of medium as a control was injected i.v. 24h after kidney transplantation. Serum was collected for creatinine concentration detection at 14 d after transplantation. Dendritic cells (DCs) phenotype and miR-146a expression level in plant was identified. Immature DCs (iDCs) and mature DCs (mDCs) were derived from monocytes. MVs were separated from BM-MSCs. RESULTS: BM-MSCs positive for CD29 (95.8%) and CD44 (94.7%) were cultured and confirmed to prolong the allogenic kidney graft survival in mice. Importantly, the expression of miR-146a increased significantly in DCs of BM-MSCs-treated allogenic kidney. Moreover, both BM-MSCs and MVs derived from BM-MSCs enhanced miR-146a expression in iDCs and mDCs in vitro. Furthermore, MVs substantially reduced IL-12 mRNA expression and IL-12 production of mDCs whereas this action was reversed by miR-146a silencing. MiR-146a silencing also abrogated the MVs-induced decrease in serum creatinine, reduction of immature DCs phenotype in transplant and increase in miR-146a expression level. CONCLUSION: In summary, our data suggested that the BM-MSCs-derived MVs improved allogenic kidney transplantation survival through inhibiting DCs maturity by miR-146a. CI - Copyright (c) 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved. FAU - Wu, Xiao-Qiang AU - Wu XQ AD - Department of Urology, Henan Provincial People's Hospital, Zhengzhou 450003, China. FAU - Yan, Tian-Zhong AU - Yan TZ AD - Department of Urology, Henan Provincial People's Hospital, Zhengzhou 450003, China. Electronic address: yantzhong666@163.com. FAU - Wang, Zhi-Wei AU - Wang ZW AD - Department of Urology, Henan Provincial People's Hospital, Zhengzhou 450003, China. FAU - Wu, Xuan AU - Wu X AD - Department of Urology, Henan Provincial People's Hospital, Zhengzhou 450003, China. FAU - Cao, Guang-Hui AU - Cao GH AD - Department of Urology, Henan Provincial People's Hospital, Zhengzhou 450003, China. FAU - Zhang, Chan AU - Zhang C AD - Department of Urology, Henan Provincial People's Hospital, Zhengzhou 450003, China. LA - eng PT - Journal Article DEP - 20170928 PL - Netherlands TA - Immunol Lett JT - Immunology letters JID - 7910006 RN - 0 (MicroRNAs) RN - 0 (Mirn146 microRNA, mouse) RN - 0 (RNA, Small Interfering) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - Bone Marrow Cells/*physiology MH - Cell Differentiation MH - Cell-Derived Microparticles/*metabolism MH - Cells, Cultured MH - Dendritic Cells/*physiology MH - Down-Regulation MH - Graft Survival/genetics MH - Interleukin-12/genetics/metabolism MH - *Kidney Transplantation MH - Mesenchymal Stem Cells/*metabolism/*physiology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - MicroRNAs/genetics/*metabolism MH - RNA, Small Interfering/genetics MH - Transplantation, Homologous OTO - NOTNLM OT - Fas OT - IL-12 OT - iDCs OT - mDCs EDAT- 2017/10/01 06:00 MHDA- 2018/02/07 06:00 CRDT- 2017/10/01 06:00 PHST- 2017/02/07 00:00 [received] PHST- 2017/09/05 00:00 [revised] PHST- 2017/09/25 00:00 [accepted] PHST- 2017/10/01 06:00 [pubmed] PHST- 2018/02/07 06:00 [medline] PHST- 2017/10/01 06:00 [entrez] AID - S0165-2478(17)30060-3 [pii] AID - 10.1016/j.imlet.2017.09.010 [doi] PST - ppublish SO - Immunol Lett. 2017 Nov;191:55-62. doi: 10.1016/j.imlet.2017.09.010. Epub 2017 Sep 28.