RESPONSE OF RENAL CELLS IN INTERSTITIAL NEPHRITIS

描述(改编自调查员摘要)：外观 间质性肾炎在自然历史中是一种预期的发展 所有形式的进行性肾功能衰竭。调查人员一直在 用一种实验模型研究这种炎症过程 小鼠免疫介导性间质性肾炎称为抗肾小管炎 基底膜(α-TBM)病。产生原发免疫损伤 在这个模型中，T细胞和抗体(AlphaTMB-Ab/Alpha3M-1-Ab) 靶向近端表达的小管靶抗原(3M-1) 肾小管上皮。组织学损伤是通过形成 间质单个核细胞渗入，随后引发 进行性纤维化伴肾小管萎缩。这一现象的出现 导致结构性损伤的自身免疫过程是复杂的产物 生化事件依赖于两个交互组件；一个 成分是发展成一种破坏性的肾炎免疫 回应。另一个成分是小管的反应-- 间质至单核侵入。长期的目的和目标 对这一应用的研究一直集中在后一个问题上。 在目前的更新中，他们选择性地集中在几个 基本的，炎症相关的蛋白质系统，调节 免疫可见性、组织边界、细胞大小和表型 靶向肾小管上皮细胞及其相关的成纤维细胞。超过了 当然，在过去的几年里，他们的工作可以被提炼成 跟踪到四个关键领域：其中一个领域是确定如何 MHC-II类基因在肾小管上皮细胞中受到调控；第二个区域 一直在确定IV型胶原基因是如何在 基底膜重塑；第三个方面已经理解了 肾小管肥大的分子机制及细胞如何扩大 可能影响致肾炎抗原的表达；以及第四 该领域一直在开发抗体和分子探针，可以 专门用于鉴定肾小管间质成纤维细胞。这些 四个项目主题共同架起了遗传学和 生物化学与基础病理生理学，以便更好地辨别重大 导致间质组织结构异常变化的过程。 研究人员的实验依赖于体外和体内两种方式 技术，以便汇编一个关于这一问题的全面数据库 这些技术包括使用细胞培养， 放射免疫分析、cdna克隆、嵌合报告基因构建、凝胶 迟滞分析，DNA足迹，转基因替换，真核生物 转染法和反义抑制法。他们相信他们的方法和 他们的分析水平将导致更好地理解 体细胞对免疫事件的关键反应可能提供新的 关于形成合理的改进策略的见解 间质损伤的治疗。

DESCRIPTION (Adapted from investigator's abstract): The appearance of interstitial nephritis is an expected development in the natural history of all forms of progressive renal failure. The investigators have been studying this inflammatory process using an experimental model of immune-mediated interstitial nephritis in mice called anti-tubular basement membrane (alphaTBM) disease. Primary immune injury is produced in this model by T cells and antibodies (alphaTMB-Ab/alpha3M-1-Ab) which are directed at a tubular target antigen (3M-1) expressed by proximal tubular epithelium. Histologic damage occurs through the formation of interstitial mononuclear cell infiltrates that subsequently invoke a progressive fibrogenesis with tubular atrophy. The emergence of this autoimmune process rendering structural damage is a product of complex biochemical events that depend on two interactive components; one component is the development of a destructive nephritogenic immune response. The other component is the reaction of the tubulo- interstitium to mononuclear intrusion. The long term purpose and goals of this application have been focused on the latter issue. In their current renewal they have concentrated selectively on several fundamental, inflammation-relevant protein systems which modulate the immunologic visibility, tissue boundaries, cell size, and phenotype of target tubular epithelium and their associated fibroblasts. Over the course of the last few years their work can be distilled down and tracked into four critical areas: one area has been to determine how MHC class II genes are regulated in tubular epithelium; the second area has been to determine how type IV collagen genes are modulated during basement membrane remodelling; the third area has been to understand the molecular mechanisms of tubular hypertrophy and how cellular enlargement may influence the expression of nephritogenic antigens; and the fourth area has been to develop antibodies and molecular probes which can be used specifically to identify tubulo-interstitial fibroblasts. These four project themes collectively bridge the disciplines of genetics and biochemistry with basic pathophysiology in order to better discern major processes leading to aberrant structural change in interstitial tissue. The investigators' experiments rely on both in vitro and in vivo technologies in order to assemble a comprehensive database on this subject; these technologies include the use of cell culture, radioimmunoassay, cDNA cloning, chimeric reporter gene constructs, gel retardation assays, DNA footprinting, transgene replacement, eurkaryotic transfection, and antisense inhibition. They believe their approach and the level of their analysis will lead to a better comprehension of critical somatic cell responses to immune events that may offer new insights regarding the formation of rational strategies for improved treatment of interstitial injury.