MECHANISMS OF TUBULOINTERSTITIAL FIBROSIS
MECHANISMS OF TUBULOINTERSTITIAL FIBROSIS
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DOI：
10.1038/ki.1991.63
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发表时间：
1991-03-01
影响因子：
19.6
通讯作者：
HAVERTY, T
中科院分区：
文献类型：
--
作者：
KUNCIO, GS;NEILSON, EG;HAVERTY, T
肾脏的正常结构和生物学功能取决于细胞和细胞外基质相互作用的整合网络。细胞外基质，除了其在肾组织组织中的作用之外，还为流体和蛋白质运动提供结构尺寸，生理系统通过所述结构尺寸操作以改变离子和大分子的过滤，或改变肾细胞的大小、增殖和生物表达[1]。因此，肾细胞外环境构成周围组织成分的主要通讯和信号处理途径。尽管对细胞外基质的特性和了解不多，但分子和细胞生物学的最新进展为进一步分析这一主题提供了多种新的实验方法[2-5]。在这些过程中，细胞-细胞接触[6]和细胞-基质粘附[7]在空间和时间环境中由一组日益丰富的基质相关细胞因子介导。这些相互作用的事件及其调节级联提供了发育中的肾脏内的结构组织的优雅重塑，它们在成年生活中的稳态维持和周转，以及它们在再生过程不再能够重建幼稚组织时的长期炎症期间的闭塞。一般来说，可能对肾单位和肾脏的功能产生重要影响[8]。这些变化可能伴随肾损伤，或作为多种病因事件的后遗症出现，包括偏离遗传野生型、新的代谢紊乱、免疫反应改变或药物的使用，也许最常见的由长期损伤引起的细胞外基质地形图紊乱是纤维化（表1）。这代表了终末期肾病的主要病变，其特征在于多种自分泌和旁分泌因子的精细化，这些因子影响几种细胞组分、它们的细胞增殖和迁移以及它们对基质组分沉积的净贡献，纤维化过程的稳态作用难以评估，因为它提供了结构上的成功，失败一方面，它代表了一种补偿机制，其启动以维持组织的结构完整性，以抑制炎症反应的有害后果，并募集和刺激修复受损组织和随后恢复功能所必需的细胞。然而，纤维化也可以反映慢性炎症事件的无情后遗症。由此产生的组织结构的破坏和破坏，以及随后在肾脏内的局部和远端部位的功能丧失可能具有广泛的临床意义。进行性纤维化，因此，可以被看作是一个正常的恢复过程，已经偏离重塑组织在一个异常的fashion. Otherwise允许的扩展，尽管他们的显着的临床影响，在肾脏局部运作的纤维化机制并没有特别好地理解在目前的时间。在比较的基础上，对于其他器官系统，特别是肝脏、肺和皮肤[9-11]，存在更多信息的文献，其中几种实验范例已被广泛利用。有必要对......有更深入的了解。
The normal architecture and biologic function of the kidney depends on an integrated network of cellular and extracellular matrix interactions. The extracellular matrix, in addition to its role in the organization of renal tissue, also provides structural dimensions for fluid and protein movement through which physiologic systems operate to modify the filtration of ions and macromolecules, or to alter the size, proliferation and biological expressions of renal cells [1], Thus, the renal extracellular milieu constitutes the primary communication and signal processing pathway for the constituents of surrounding tissue. Although poorly characterized and poorly understood, recent advances in molecular and cellular biology have provided a variety of new experimental approaches from which to further analyze this subject matter [2–5].Several highly dynamic processes are thought to modulate the integrity of the extracellular matrix as well as its associated cellular components. Among these processes are cell-cell contact [6] and cell-matrix adhesion [7] mediated, in both spatial and temporal circumstances, by an increasingly abundant set of matrix-relevant cytokines. These interactive events, and their regulatory cascade, provide for the elegant remodelling of structural tissues within developing kidney, their homeostatic maintenance and turnover in adult life, as well as their obliteration during prolonged inflammation when regenerative processes are no longer capable of recreating naive tissues.Any alteration in the composition and structure of the extracellular matrix is, therefore, likely to have important consequences for the function of the nephron, and kidney, in general [8]. Such changes may accompany renal injury, or appear as sequelae of a variety of etiologic events, including deviation from the genetic wild-type, new metabolic disturbances, altered immunological responses, or the use of pharmaceuticals.Perhaps the most commonly recognized disturbance in the topography of extracellular matrix resulting from prolonged injury is fibrosis (Table 1). This represents the major lesion of end-stage renal disease, and is characterized by the elaboration of a variety of autocrine and paracrine factors affecting several cellular components, their cellular proliferation and migration, and their net contribution to the deposition of matrix components, particularly the interstitial collagens.The homeostatic role of the fibrogenic process is difficult to evaluate because it provides structural success mixed with architectural failure. On one hand, it represents a compensatory mechanism initiated to maintain the structural integrity of tissue, to contain the deleterious consequences of inflammatory reactions, and to recruit and stimulate cells necessary for the repair of damaged tissue and subsequent restoration of function. Fibrogenesis, however, can also reflect the relentless sequelae of chronic inflammatory events. The resultant disruption and destruction of tissue architecture, and the subsequent loss of function at both local and distant sites within the kidney can have widespread clinical implications. Progressive fibrogenesis, therefore, can be viewed as a permissive extension of normal restorative processes which have deviated to remodel tissue in an aberrant fashion.Oddly enough, despite their significant clinical impact, fibrogenic mechanisms operating locally in the kidney are not particularly well understood at the present time. On a comparative basis, a more informative literature exists for other organ systems, particularly the liver, lung, and skin [9–11] where several experimental paradigms have been extensively exploited. There is a need for a more thorough comprehension of the …