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The Role of Angiotensin II Receptor Subtype in Ocular Injury

血管紧张素 II 受体亚型在眼损伤中的作用

基本信息

批准号：
14370559
负责人：
OHASHI Yuichi
金额：
$ 3.52万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370559/
关键词：
angiotensin wound healing receptor conjunctiva cornea collagen TIMP MMP

项目摘要

Angiotensin II (Ang II) plays an important role in the regulation of cardiovascular structure and hemodynamics. Two major Ang II receptor subtypes, named type 1 (AT_1) and type 2 (AT_2) receptors, have been previously reported. Recent studies suggest that Ang II regulates wound healing process through these receptors. However, the detailed mechanism is not clarified We investigated the role of AT_1 and AT_2 receptor subtypes in ocular injury using wound healing model.1.Subconjunctival wound healing : Wound healing model was developed by subconjuncival blunt dissection in male wild type (WT ; C57BL/6J), AT_<1a> null (AT_<1a>KO) and AT_2 null (AT_2KO) mice. Subconjunctival injury induced collagen deposition. Subconjunctival collagen deposition detected by histological analysis at 14 days after injury was higher in AT_2KO mice than in WT mice, but it was lower than in AT_<1a>KO mice than in WT mice. The level of mRNA for type 1 collagen at 7 days was increased in subconjunctival tissue including conjunctiva after injury. This increase was significantly higher in AT_2KO mice, but it was lower than in AT_<1a>KO mice than in WT mice. To examine the mechanism of action of AT1 and AT2 receptors on collagen synthesis regulation, we assayed the expression of TIMP-1. The level of mRNA was also increased at 12 hours after injury after subconjuntival damage. However, the increase in TIMP-1 expression was significantly higher in AT_<1a>KO mice, but lower than in AT_2KO mice than in WT mice.2. Corneal epithelial wound healing : Corneal epithelial wound healing model was made by eximer lazar in male WT and AT_<1a>KO mice. AT_<1a>KO mice delayed corneal epithelial wound healing compared to WT mice. The BrdU index in epithelial cells was lower in the AT_<1a>KO mice than in the WT mice.These results suggest that AT_1 and AT2 receptor subtypes play an important role in the regulation of ocular injury.

血管紧张素II（Angiotensin II，Ang II）在心血管结构和血流动力学的调节中起重要作用。血管紧张素Ⅱ受体有两种亚型，即1型（AT_1）和2型（AT_2）受体。近年来的研究表明，血管紧张素II通过这些受体调节创伤愈合过程。1.结膜下伤口愈合：采用结膜下钝性分离法建立了雄性野生型（WT ; C57 BL/6 J）、AT_<1a>null（AT_<1a>KO）和AT_2 null（AT_2KO）小鼠的伤口愈合模型。结膜下损伤诱导胶原蛋白沉积。损伤后14天，组织学检查显示AT_2KO小鼠结膜下胶原沉积高于WT小鼠，但低于AT_<1a>KO小鼠。伤后7天，包括结膜在内的结膜下组织中1型胶原mRNA的水平增加。这种增加在AT_2KO小鼠中显著更高，但低于AT_<1a>KO小鼠中的WT小鼠。为了研究AT 1和AT 2受体对胶原合成调节的作用机制，我们检测了TIMP-1的表达。结膜下损伤后12小时mRNA水平也升高。然而，TIMP-1表达的增加在AT_ KO小鼠中显著高于<1a>WT小鼠，但低于AT_2KO小鼠.角膜上皮伤口愈合：通过准分子lazar在雄性WT和AT_ KO小鼠中制备角膜上皮伤口愈合模型<1a>。与<1a>WT小鼠相比，AT_ KO小鼠延迟角膜上皮伤口愈合。AT_ KO小鼠眼上皮细胞BrdU指数低于<1a>WT小鼠，提示AT_1和AT_2受体亚型在眼损伤的调节中起重要作用。