miR-125a-5p attenuates macrophage-mediated vascular dysfunction by targeting Ninjurin1.
miR-125a-5p attenuates macrophage-mediated vascular dysfunction by targeting Ninjurin1.
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DOI：
10.1038/s41418-021-00911-y
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发表时间：
2022-06
影响因子：
12.4
通讯作者：
Lee, Hyo-Jong
中科院分区：
文献类型：
--
作者：
Hwang, Su Jung;Ahn, Bum Ju;Shin, Min-Wook;Song, Ye-Seul;Choi, Youngbin;Oh, Goo Taeg;Kim, Kyu-Won;Lee, Hyo-Jong
Ninjurin1 （Ninj1）是一种粘附分子，调节巨噬细胞在玻璃体退化、多发性硬化和动脉粥样硬化中的功能。然而，其生物学意义及其在血管网络完整性中的作用机制尚未得到研究。在这项研究中，我们研究了Ninj1在生理（出生后血管形成）和病理（内毒素介导的炎症和糖尿病）条件下的作用，并制定了一种在病理条件下使用特定微（mi） rna调节Ninj1的策略。nin1缺陷小鼠在出生后发育过程中表现出玻璃体退化、尖端细胞形成、视网膜血管化面积、巨噬细胞募集和内皮细胞凋亡减少，导致血管网络形成延迟。通过miRanda算法和表达模式的比较，选择了5个可能靶向Ninj1的mirna。其中，miR-125a-5p对Ninj1表达有较深的抑制作用，miR-125a-5p mimic抑制了巨噬细胞的细胞间和细胞间基质粘附以及Ninj1介导的促炎因子的表达。此外，miR-125a-5p模拟物在体内抑制内毒素诱导的炎症和链脲霉素诱导的糖尿病中巨噬细胞向炎症视网膜募集。特别是，miR-125a-5p模拟显著减轻糖尿病视网膜病变的血管渗漏。综上所述，这些研究结果表明，Ninj1在巨噬细胞介导的血管完整性中起关键作用，miR-125a-5p在炎症性疾病和糖尿病视网膜病变的管理中作为Ninj1的新调节剂。
Ninjurin1 (Ninj1), an adhesion molecule, regulates macrophage function in hyaloid regression, multiple sclerosis, and atherosclerosis. However, its biological relevance and the mechanism underlying its function in vascular network integrity have not been studied. In this study, we investigated the role of Ninj1 in physiological (postnatal vessel formation) and pathological (endotoxin-mediated inflammation and diabetes) conditions and developed a strategy to regulate Ninj1 using specific micro (mi)RNAs under pathological conditions. Ninj1-deficient mice exhibited decreased hyaloid regression, tip cell formation, retinal vascularized area, recruitment of macrophages, and endothelial apoptosis during postnatal development, resulting in delayed formation of the vascular network. Five putative miRNAs targeting Ninj1 were selected using the miRanda algorithm and comparison of expression patterns. Among them, miR-125a-5p showed a profound inhibitory effect on Ninj1 expression, and miR-125a-5p mimic suppressed the cell-to-cell and cell-to-matrix adhesion of macrophages and expression of pro-inflammatory factors mediated by Ninj1. Furthermore, miR-125a-5p mimic inhibited the recruitment of macrophages into inflamed retinas in endotoxin-induced inflammation and streptozotocin-induced diabetes in vivo. In particular, miR-125a-5p mimic significantly attenuated vascular leakage in diabetic retinopathy. Taken together, these findings suggest that Ninj1 plays a pivotal role in macrophage-mediated vascular integrity and that miR-125a-5p acts as a novel regulator of Ninj1 in the management of inflammatory diseases and diabetic retinopathy.
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DOI：
10.1016/j.bbrc.2012.10.099
发表时间：
2012-11-30
影响因子：
3.1
作者：
Ahn, Bum Ju;Le, Hoang;Kim, Kyu-Won
通讯作者：
Kim, Kyu-Won
影响因子：
9.8
作者：
Elayappan, Banumathi;Ravinarayannan, Haribalaganesh;Gurunathan, Sangiliyandi
通讯作者：
Gurunathan, Sangiliyandi
影响因子：
4.6
作者：
Choi S;Woo JK;Jang YS;Kang JH;Hwang JI;Seong JK;Yoon YS;Oh SH
通讯作者：
Oh SH
影响因子：
20.3
作者：
Fantin, Alessandro;Vieira, Joaquim M.;Ruhrberg, Christiana
通讯作者：
Ruhrberg, Christiana
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C