CHEMICAL PATHOLOGY AND RENAL REPAIR

组织修复在生物反应中起着重要作用。 活化的环境化学物质对肾脏的毒性损害 活性化学物质。肾脏是化学物质的主要靶点。 毒素，因为它在异种生物代谢中的作用。虽然它的机制 肾毒素的激活和细胞毒性越来越明显， 人们对化学损伤的修复机制知之甚少。我们确实知道， 近端小管上皮细胞通过取代死亡来修复损伤 但是，我们还不知道剩余细胞的增殖情况。 是什么控制了增殖反应。因为修复组织 在整体上，伤害可能与激活步骤同等重要 肾脏对环境毒素的反应，重要的是要 了解维修流程。有了这些知识，我们未来的目标将是 将评估持续暴露在环境污染物中的影响 关于修复过程本身。这一点至关重要，因为环境 接触往往是慢性的，而不是急性的，并且有能力抑制 修复可能会导致器官损伤。 我们的目标是阐明肾脏组织修复的机制。 (肾性修复)。我们建议监管机构，包括增长因素 和细胞外基质，控制修复过程的各个阶段：1) 进入细胞周期，2)细胞生长，3)停止生长，以及 4)分化。已经建立了体内每个阶段的标记 AS有一种培养大鼠肾近端小管上皮细胞的方法 它们表达了相同的生长和分化标志 恰如其分。因此，体内和体外相结合的方法 将用于协助调查以及交叉核对和核实 结果。与各阶段相关的生长因子表达变化 肾源性修复(由标记物鉴定)将在活体内确定 使用cDNA探针和/或抗体。一旦这些因素被 确定了它们控制细胞生长和 使用组织培养模型可以在体外阐明分化。 蛋白激酶是生长因子的重要调节因子。 因此，蛋白激酶在肾源性修复中的作用将 要下定决心。具体地说，生长因子调节的底物 蛋白激酶将在肾上皮细胞中被识别。最后， 细胞外基质在调控肾细胞功能中的作用 通过确定以下表达式来评估差异化 培养的肾上皮细胞分化标记物。

Tissue repair plays an important role in the biological response to nephrotoxic damage by environmental chemicals which are activated to reactive chemical species. The kidney is a major target for chemical toxins due to its role in xenobiotic metabolism. Though the mechanisms of nephrotoxin activation and cellular toxicity are becoming more clear, the mechanism for repair of chemical damage are poorly understood. We do know, that the proximal tubule epithelial cells repair damage by replacing dead cells through, proliferation of remaining cells, however, we do not know what controls the proliferative response. Since repairing the tissue damage may be of equal importance to the activation step in the overall response of the kidney to environmental toxins, it is important to understand the repair process. With this knowledge, our future goal will be to assess the effect of continued exposure to environmental pollutants on the repair process itself. This is critical since environmental exposure tend to be chronic rather than acute, and the ability to inhibit repair may contribute to organ damage. Our goal is to elucidate the mechanisms of tissue repair in the kidney (nephrogenic repair). We propose that regulators, Including growth factors and extracellular matrix, control the phases of the repair process: 1) entry into the cell cycle, 2) growth of cells, 3) cessation of growth, and 4) differentiation. Markers for each phase in vivo have been established as has a method for culturing rat kidney proximal tubule epithelial' cells which express the same markers for growth and differentiation appropriately. Therefore, a combination of in vivo and in vitro approaches will be used to facilitate the investigations and to cross-check and verify results. Changes in growth factor expression associated with each phase of nephrogenic repair (as identified by markers) will be determined in vivo using cDNA probes and/or antibodies. Once these factors have been identified, the mechanisms through which they control cell growth and differentiation can be elucidated in vitro using the tissue culture model. Protein kinases play a major role as regulators of growth factor action, therefore,, the role of protein kinases in nephrogenic repair will be determined. Specifically, substrates for growth factor-regulated protein kinases will be identified in kidney epithelial cells. Finally, the role of extracellular matrix in controlling the ability of kidney cells to differentiate will be evaluated by determining the expression of differentiation markers by the cultured renal epithelial cells.