KERATOCYTE REGULATION IN CORNEAL REPAIR

描述：角膜细胞在创伤修复中起重要作用 角膜 开始角膜愈合过程的关键步骤是 通常静止的角膜细胞网络的戏剧性转变 转化成活化的纤维细胞 这些，反过来，分化成富含肌动蛋白的 肌成纤维细胞，其在伤口闭合中起关键作用。 主要研究者有 开发了一种体外模型，该模型再现了角膜细胞向 成纤维细胞，然后是肌成纤维细胞。 这一提议的核心假设是肌成纤维细胞 创伤和愈合过程中的分化是由相互作用控制的， 三个主要因素：细胞间接触的丧失， TGF-β和改变的细胞-基质相互作用。 研究人员提出：（1） 一个角膜成纤维细胞与另一个角膜成纤维细胞分离， 创伤引发一系列生化/分子事件， 成纤维细胞对TGF-β有反应，并分化为 2）细胞间接触的重建减弱了肌成纤维细胞的增殖。 对TGF-β的细胞应答;和3）基质产生的信号是额外的， 肌成纤维细胞分化和功能的必需调节剂。 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 分化 2. 反应中缺乏肌成纤维细胞分化 融合成纤维细胞中TGF-β的表达下调是由于 细胞表面TGF-β受体。 3. 连接蛋白表达的改变 在钙粘蛋白表达之前， 在体内的伤害。 4. 来自替代性纤连蛋白的基质产生的信号 同种型和改变的整合素表达是 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.