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（ANG II）在心血管结构和血流动力学的调节中起重要作用。先前已经报道了两种称为1型（AT_1）和2型（AT_2）受体的主要ANG II受体亚型。最近的研究表明，ANG II通过这些受体调节伤口愈合过程。但是，尚未澄清详细的机制，我们研究了使用伤口愈合模型在眼部损伤中AT_1和AT_2受体亚型的作用。1。subconjunctivalival伤口愈合：伤口愈合模型是由雄性野生型（WT; C57BL/ C57BL/ C57BL/ C57BL/ C57BL/ C57BL/ blunt解剖开发）开发的。 6j），at_ <1a> null（at_ <1a> ko）和at_2 null（at_2ko）小鼠。膜下损伤诱导的胶原蛋白沉积。通过在AT_2KO小鼠损伤后14天通过组织学分析检测到的胶原蛋白沉积比在WT小鼠中高的胶原蛋白沉积高，但它低于AT_ <1A> ko小鼠中的小鼠。在包括损伤后，包括结膜的结膜组织中，在7天时1型胶原蛋白的mRNA水平增加。 AT_2KO小鼠中的这种增加明显高，但低于AT_ <1A> KO小鼠中的增加。为了检查AT1和AT2受体对胶原蛋白合成调节的作用机理，我们测定了TIMP-1的表达。损伤后12小时后，mRNA的水平也升高。然而，AT_ <1a> KO小鼠的TIMP-1表达的增加显着高，但低于AT_2KO小鼠中的TIMP-1表达的增加高于WT小鼠2。角膜上皮伤口愈合：角膜上皮伤口愈合模型是由雄性WT和AT_ <1A> KO小鼠制成的。与WT小鼠相比，AT_ <1A> KO小鼠延迟了角膜上皮伤口愈合。 AT_ <1a> KO小鼠中上皮细胞中的BRDU指数低于WT小鼠。这些结果表明AT_1和AT2受体亚型在调节眼损伤中起重要作用。