Deletion of the FHL2 gene attenuating neovascularization after corneal injury.

Deletion of the FHL2 gene attenuating neovascularization after corneal injury.
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DOI:
10.1167/iovs.08-2209
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发表时间:
2008-12
影响因子:
4.4
通讯作者:
Chen J
Chen J
中科院分区:
医学2区
文献类型:
--
作者:
Chu PH;Yeh LK;Lin HC;Jung SM;Ma DH;Wang IJ;Wu HH;Shiu TF;Chen J

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含四个半 LIM 结构域的蛋白 2 (FHL2) 是仅四个半 LIM 结构域 (FHL) 基因家族的成员。尽管 FHL2 在角膜中表达,但其在血管生成中的作用尚不清楚。本研究的目的是探讨 FHL2 基因在化学损伤后角膜血管生成中的作用。 FHL2-LacZ 敲入小鼠用于追踪角膜损伤前后 FHL2 基因的表达。比较了 FHL2 缺失小鼠和经历角膜和角膜缘上皮化学和机械剥脱的野生型小鼠之间的角膜血管生成。通过 CD31 染色评估新生长血管密度,并使用图像分析软件进行分析。通过蛋白质印迹法测定血管内皮生长因子(VEGF)和环氧合酶(COX)-2蛋白的水平。 FHL2-LacZ 敲入小鼠角膜组织的 β-半乳糖苷酶染色显示,角膜损伤后角膜上皮中 FHL2 基因表达上调。损伤后十天,在对照小鼠和 FHL2 缺失小鼠中观察到角膜新生血管形成。发现 FHL2 缺失小鼠损伤组的新角膜血管密度低于野生型小鼠损伤组。 Western blot分析显示,FHL2缺失小鼠和野生型小鼠化学损伤后VEGF和COX-2蛋白水平较高。然而,FHL2缺失小鼠中上调的VEGF蛋白显着低于野生型小鼠。本研究中发现 FHL2 缺失小鼠中化学诱导的角膜血管生成减少,表明 FHL2 蛋白在抑制炎症血管生成中发挥作用。
The four-and-one-half LIM domain-containing protein2 (FHL2) is a member of the four-and-a-half LIM domain-only (FHL) gene family. Although FHL2 is expressed in the cornea, its role in angiogenesis is unclear. The aim of this study was to investigate the role of the FHL2 gene in corneal angiogenesis after chemical injury. FHL2-LacZ knock-in mice were used to trace FHL2 gene expression before and after corneal injury. Corneal angiogenesis between FHL2-null mice and wild-type mice that underwent chemical and mechanical denudation of corneal and limbal epithelium were compared. New growth vessel density was assessed by CD31 staining and was analyzed using image analysis software. Levels of vascular endothelial growth factor (VEGF) and cyclooxygenase (COX)-2 proteins were determined by Western blot assay. β-Galactosidase staining of corneal tissue in FHL2-LacZ knock-in mice revealed that FHL2 gene expression is upregulated in the corneal epithelium after corneal injury. Ten days after injury, corneal neovascularization was observed in control and FHL2-null mice. New corneal vessel density was found to be lower in the FHL2-null mice injury group than in the wild-type mice injury group. Western blot analysis showed that VEGF and COX-2 protein levels were higher after chemical injury in FHL2-null mice and wild-type mice. However, the upregulated VEGF protein was significantly lower in the FHL2-null mice than in the wild-type mice. The decreased chemical-induced corneal angiogenesis found in the FHL2-null mice in this study indicated that FHL2 protein plays a role in inhibiting inflammatory angiogenesis.
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发表时间: 2004-02-01
影响因子: 5.3
作者:
Purcell, NH;Darwis, D;Molkentin, JD
通讯作者: Molkentin, JD
DOI: 10.1152/ajpregu.00108.2004
发表时间: 2004-11-01
影响因子: 2.8
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发表时间: 2000-10-01
影响因子: 5.3
作者:
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DOI: 10.1016/s0303-7207(01)00463-4
发表时间: 2001-06-20
影响因子: 4.1
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DOI: 10.1167/iovs.02-0685
发表时间: 2003-02-01
影响因子: 4.4
作者:
Ambati, BK;Anand, A;Ambati, J
通讯作者: Ambati, J