A Novel Hypoxia-inducible Factor 1α Inhibitor KC7F2 Attenuates Oxygen-induced Retinal Neovascularization.
A Novel Hypoxia-inducible Factor 1α Inhibitor KC7F2 Attenuates Oxygen-induced Retinal Neovascularization.
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一种新型缺氧诱导因子 1α 抑制剂 KC7F2 减弱氧诱导的视网膜新生血管形成
DOI：
10.1167/iovs.63.6.13
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发表时间：
2022-06-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
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作者：
KC 7 F2是一种新型的抑制低氧诱导因子1α（HIF 1 α）翻译的分子化合物。据报道，它具有潜在的抗血管生成作用。我们假设KC 7 F2可以抑制氧诱导的视网膜新生血管（RNV）。本研究的目的就是为了验证这一假设。使用C57 BL/6 J小鼠和Sprague-Dawley大鼠中的氧诱导视网膜病变（OIR）模型进行体内研究。腹腔注射KC 7 F2后，通过免疫荧光和苏木精-伊红染色检测RNV。免疫荧光检测视网膜炎症。采用EdU掺入法、Kit-8细胞计数法、划痕法、transwell法和Matrigel法观察KC 7 F2对血管内皮生长因子（VEGF）诱导的人脐静脉内皮细胞（HUVEC）增殖、迁移和管腔形成的影响。Western blot检测蛋白表达。KC 7 F2治疗（10 mg/kg/d）在OIR小鼠中显著减弱病理性新生血管形成，并减少视网膜前新生血管细胞核的数量，而不改变无血管面积，这在OIR大鼠中显示出相同的趋势。一致地，在KC 7 F2干预（10 µM）后，VEGF诱导的HUVEC中的细胞增殖受到抑制，这与OIR小鼠视网膜中观察到的趋势一致。同时，KC 7 F2抑制VEGF诱导的HUVEC迁移和管形成，并降低视网膜中共定位新生血管区域的白细胞和小胶质细胞的密度。此外，在OIR小鼠视网膜和缺氧诱导的HUVEC中激活的HIF 1 α-VEGF通路被KC 7 F2处理抑制。目前的研究表明，KC 7 F2能够通过HIF 1 α-VEGF途径有效抑制RNV，提示其可能是一种有效的治疗RNV的药物。
KC7F2 is a novel molecule compound that can inhibit the translation of hypoxia-inducible factor 1α (HIF1α). It has been reported to exhibit potential antiangiogenic effect. We hypothesized that KC7F2 could inhibit oxygen-induced retinal neovascularization (RNV). The purpose of this study was to investigate this assumption. Oxygen-induced retinopathy (OIR) models in C57BL/6J mice and Sprague-Dawley rats were used for in vivo study. After intraperitoneal injections of KC7F2, RNV was detected by immunofluorescence and hematoxylin and eosin staining. Retinal inflammation was explored by immunofluorescence. EdU incorporation assay, cell counting kit-8 assay, scratch test, transwell assay, and Matrigel assay were used to evaluate the effect of KC7F2 on the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVEC) induced by vascular endothelial growth factor (VEGF) in vitro. Protein expression was examined by Western blot. KC7F2 treatment (10 mg/kg/d) in OIR mice significantly attenuated pathological neovascularization and decreased the number of preretinal neovascular cell nuclei, without changing the avascular area, which showed the same trends in OIR rats. Consistently, after the KC7F2 intervention (10 µM), cell proliferation was inhibited in VEGF-induced HUVEC, which was in agreement with the trend observed in the retinas of OIR mice. Meanwhile, KC7F2 suppressed VEGF-induced HUVEC migration and tube formation, and decreased the density of leukocytes and microglia colocalizing neovascular areas in the retinas. Moreover, the HIF1α–VEGF pathway activated in retinas of OIR mice and hypoxia-induced HUVEC, was suppressed by KC7F2 treatment. The current study revealed that KC7F2 was able to inhibit RNV effectively via HIF1α–VEGF pathway, suggesting that it might be an effective drug for RNV treatment.
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DOI：
10.1158/1078-0432.ccr-08-3180
发表时间：
2009-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Narita T;Yin S;Gelin CF;Moreno CS;Yepes M;Nicolaou KC;Van Meir EG
通讯作者：
Van Meir EG
影响因子：
13.7
作者：
Hartnett, M. Elizabeth
通讯作者：
Hartnett, M. Elizabeth
SOHLH2 通过下调乳腺癌中 HIF1α 的表达来抑制血管生成
影响因子：
5.2
作者：
Cui, Weiwei;Xiao, Yunling;Hao, Jing
通讯作者：
Hao, Jing
影响因子：
8.2
作者：
Lin M;Chen Y;Jin J;Hu Y;Zhou KK;Zhu M;Le YZ;Ge J;Johnson RS;Ma JX
通讯作者：
Ma JX
影响因子：
8.1
作者：
Eadie, Brennan D.;Etminan, Mahyar;Mikelberg, Frederick S.
通讯作者：
Mikelberg, Frederick S.