MicroRNA-30b Is Both Necessary and Sufficient for Interleukin-21 Receptor-Mediated Angiogenesis in Experimental Peripheral Arterial Disease.
MicroRNA-30b Is Both Necessary and Sufficient for Interleukin-21 Receptor-Mediated Angiogenesis in Experimental Peripheral Arterial Disease.
复制标题
DOI：
10.3390/ijms23010271
复制
发表时间：
2021-12-27
影响因子：
5.6
通讯作者：
Annex BH
中科院分区：
文献类型：
--
作者：
Wang T;Yang L;Yuan M;Farber CR;Spolski R;Leonard WJ;Ganta VC;Annex BH
在小鼠后肢缺血（HLI）（一种实验性外周动脉疾病（PAD）模型）后，来自缺血肌肉的内皮细胞（EC）中的白细胞介素-21受体（IL-21R）可以上调，阻断这种配体受体途径受损的STAT3激活、血管生成和灌注恢复。基于缺血肌肉具有完整或减少的IL-21/IL21R信号传导，我们试图鉴定HLI后差异调节的mRNA和microRNA转录本。在这个比较中，200个mrna有差异表达，但只有6个microRNA (miR)/miR簇（其中只有miR-30b）在从缺血肌肉分离的EC中上调。接下来，在HLI和IL-21过表达后检查的肌红蛋白过表达转基因（MgTG） C57BL/6小鼠，血管生成更大，灌注恢复更好，组织坏死更少，miR-30b表达增加。在低氧血清饥饿培养的EC中，miR-30b的敲除减少，而miR-30b的过表达增加了il -21介导的EC的存活和血管生成。在HLI后的Il21r−/−小鼠中，miR-30b过表达与对照组相比改善了灌注恢复，减少了细胞因子信号传导3的抑制因子，miR-30b的靶点和STAT3的负调节因子。总之，miR-30b对于il -21 / il - 21r介导的血管生成是必要的和充分的，如果il - 21r无法激活，miR-30b可能是治疗PAD的一种新的治疗选择。
The interleukin-21 receptor (IL-21R) can be upregulated in endothelial cells (EC) from ischemic muscles in mice following hind-limb ischemia (HLI), an experimental peripheral arterial disease (PAD) model, blocking this ligand–receptor pathway-impaired STAT3 activation, angiogenesis, and perfusion recovery. We sought to identify mRNA and microRNA transcripts that were differentially regulated following HLI, based on the ischemic muscle having intact, or reduced, IL-21/IL21R signaling. In this comparison, 200 mRNAs were differentially expressed but only six microRNA (miR)/miR clusters (and among these only miR-30b) were upregulated in EC isolated from ischemic muscle. Next, myoglobin-overexpressing transgenic (MgTG) C57BL/6 mice examined following HLI and IL-21 overexpression displayed greater angiogenesis, better perfusion recovery, and less tissue necrosis, with increased miR-30b expression. In EC cultured under hypoxia serum starvation, knock-down of miR-30b reduced, while overexpression of miR-30b increased IL-21-mediated EC survival and angiogenesis. In Il21r−/− mice following HLI, miR-30b overexpression vs. control improved perfusion recovery, with a reduction of suppressor of cytokine signaling 3, a miR-30b target and negative regulator of STAT3. Together, miR-30b appears both necessary and sufficient for IL21/IL-21R-mediated angiogenesis and may present a new therapeutic option to treat PAD if the IL21R is not available for activation.
登录
查看更多内容
影响因子：
7.7
作者：
Li, Yongjun;Hazarika, Surovi;Annex, Brian H.
通讯作者：
Annex, Brian H.
影响因子：
168.9
作者：
Fowkes, F. Gerald R.;Rudan, Diana;Criqui, Michael H.
通讯作者：
Criqui, Michael H.
影响因子：
20.3
作者：
Bridge, Gemma;Monteiro, Rui;Boshoff, Chris
通讯作者：
Boshoff, Chris
影响因子：
10.8
作者：
Dokun, Ayotunde O.;Chen, Lingdan;Annex, Brian H.
通讯作者：
Annex, Brian H.
DOI：
10.1152/ajpheart.00803.2014
发表时间：
2015-09-01
影响因子：
4.8
作者：
Dokun, Ayotunde O.;Chen, Lingdan;Annex, Brian H.
通讯作者：
Annex, Brian H.