KERATOCYTE REGULATION IN CORNEAL REPAIR

描述：角膜基质细胞在创伤修复中起着重要作用。 眼角膜。启动角膜愈合过程的关键一步是 正常静止的角质形成细胞网络的戏剧性转变 转化为激活的成纤维细胞。这些细胞依次分化为富含肌动蛋白的细胞。 肌成纤维细胞在伤口闭合过程中起着关键作用。少年派有 开发了一种体外模型，复制了角质形成细胞到 成纤维细胞，然后是肌成纤维细胞。 这一提议的中心假设是肌成纤维细胞 损伤和愈合过程中的分化受相互作用的控制 三个主要因素：细胞-细胞接触的丧失，细胞的存在 转化生长因子-β，并改变细胞-基质相互作用。研究人员提出，1) 一种角膜成纤维细胞与另一种角膜成纤维细胞的分离 创伤引发一系列生化/分子事件，导致 成纤维细胞对转化生长因子-β的反应并分化为 肌成纤维细胞；2)细胞-细胞接触的重建减弱了 细胞对转化生长因子-β的反应；以及3)基质产生的信号是附加的， 肌成纤维细胞分化和功能的基本调节剂。 该提案的具体目的是检验以下假设：1. 缝隙连接介导的细胞间通讯调控肌成纤维细胞 差异化。2.反应中肌成纤维细胞没有分化 融合成纤维细胞对转化生长因子-β的抑制作用 细胞表面的转化生长因子-β受体。3.连接蛋白表达的变化 在钙粘素表达之前，是角膜反应的早期事件 活体内的伤人。4.来自替代纤维连接蛋白的基质产生的信号 异构体和改变的整合素表达是关键的调节器 肌成纤维细胞分化和/或功能。

DESCRIPTION: Keratocytes play an important role in repair of the wounded cornea. A critical step for initiation of the corneal healing process is the dramatic conversion of the network of normally quiescent keratocytes into activated fibroblasts. These, in turn, differentiate into actin-rich myofibroblasts which play a critical role in wound closure. The PI has developed an in vitro model that reproduces the transition of keratocytes to fibroblasts and then to myofibroblasts. The central hypothesis of this proposal is that myofibroblast differentiation during wounding and healing is controlled by the interplay of three dominant factors: the loss of cell-cell contact, the presence of TGF-B, and altered cell-matrix interaction. The researchers propose that 1) disconnection of one corneal fibroblast from another that occurs soon after wounding initiates a series of biochemical/ molecular events that causes fibroblasts to be responsive to TGF-B and to differentiate into myofibroblasts; 2) re-establishment of cell-cell contact attenuates the cellular response to TGF-B; and 3) matrix-generated signals are additional, essential modulators of myofibroblast differentiation and function. The specific aims of the proposal are to test the following hypotheses: 1. Gap junction-mediated intercellular communications regulate myofibroblast differentiation. 2. Absence of myofibroblast differentiation in response to TGF-B in confluent fibroblasts results from down-regulation of cell-surface TGF-B receptors. 3. Alterations in expression of connexins precede cadherin expression and are early events of the corneal response to wounding in vivo. 4. Matrix-generated signals from alternative fibronectin isoforms and altered integrin expression are critical modulators of myofibroblast differentiation and /or function.