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微小 RNA107 通过 HIF-1β 部分抑制内皮祖细胞的分化。

MicroRNA 107 partly inhibits endothelial progenitor cells differentiation via HIF-1β.

机构信息

Department of Cardiology, School of Medicine, Shanghai Jiao-tong University, Xin-hua Hospital, Shanghai, China.

出版信息

PLoS One. 2012;7(7):e40323. doi: 10.1371/journal.pone.0040323. Epub 2012 Jul 6.

DOI:10.1371/journal.pone.0040323
PMID:22792280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3391260/
Abstract

Endothelial progenitor cells (EPCs) play an important role in tissue repair after ischemic heart disease. In particular, the recovery of endothelial function is reliant on the ability and rate of EPCs differentiate into mature endothelial cells. The present study evaluated the effect of microRNA 107 (miR-107) on the mechanism of EPCs differentiation. EPCs were isolated from rats' bone marrow and miR-107 expression of EPCs in hypoxic and normoxic conditions were measured by real-time qualitative PCR. CD31 was analyzed by flow cytometry and eNOS was examined by real-time qualitative PCR and western blotting and these were used as markers of EPC differentiation. In order to reveal the mechanism, we used miR107 inhibitor and lentiviral vector expressing a short hairpin RNA (shRNA) that targets miR-107 and hypoxia-inducible factor-1 β (HIF-1β) to alter miR107 and HIF-1β expression. MiR-107 expression were increased in EPCs under hypoxic conditions. Up-regulation of miR-107 partly suppressed the EPCs differentiation induced in hypoxia, while down-regulation of miR-107 promoted EPC differentiation. HIF-1β was the target. This study indicated that miR-107 was up-regulated in hypoxia to prevent EPCs differentiation via its target HIF-1β. The physiological mechanisms of miR-107 must be evaluated if it is to be used as a potential anti-ischemia therapeutic regime.

摘要

内皮祖细胞 (EPCs) 在缺血性心脏病后组织修复中发挥重要作用。特别是,内皮功能的恢复依赖于 EPCs 分化为成熟内皮细胞的能力和速度。本研究评估了 microRNA 107 (miR-107) 对 EPCs 分化机制的影响。从大鼠骨髓中分离 EPCs,并通过实时定量 PCR 测量缺氧和常氧条件下 EPCs 中 miR-107 的表达。通过流式细胞术分析 CD31,通过实时定量 PCR 和 Western blot 检测 eNOS,并将其用作 EPC 分化的标志物。为了揭示机制,我们使用了 miR107 抑制剂和表达针对 miR-107 和缺氧诱导因子-1β (HIF-1β) 的短发夹 RNA (shRNA) 的慢病毒载体来改变 miR107 和 HIF-1β 的表达。EPCs 在缺氧条件下表达 miR-107。miR-107 的上调部分抑制了缺氧诱导的 EPCs 分化,而下调 miR-107 则促进了 EPC 分化。HIF-1β 是靶基因。本研究表明,miR-107 在缺氧条件下上调,通过其靶基因 HIF-1β 来防止 EPCs 分化。如果要将 miR-107 用作潜在的抗缺血治疗方案,则必须评估其生理机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/d534a5a98bdf/pone.0040323.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/28332c781777/pone.0040323.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/6fcedc2fb01a/pone.0040323.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/2c827f9983e5/pone.0040323.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/0306b736c809/pone.0040323.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/d534a5a98bdf/pone.0040323.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/28332c781777/pone.0040323.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/6fcedc2fb01a/pone.0040323.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/2c827f9983e5/pone.0040323.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/0306b736c809/pone.0040323.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a24a/3391260/d534a5a98bdf/pone.0040323.g005.jpg

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