Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure
Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure
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DOI：
10.1097/01.asn.0000067652.51441.21
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发表时间：
2003-06-01
影响因子：
13.6
通讯作者：
Bonventre, JV
中科院分区：
文献类型：
--
作者：
Bonventre, JV
与心脏或大脑相反，肾脏可以从导致细胞死亡的缺血性或毒性损伤中完全恢复。在从缺血/再灌注损伤恢复期间，存活的肾小管上皮细胞去分化和增殖，最终替换不可逆损伤的肾小管上皮细胞并恢复肾小管完整性。肾脏的修复与肾脏器官形成在DNA合成和细胞凋亡的高速率以及基因表达模式方面平行。正如增殖细胞核抗原和5-溴2 '-脱氧尿苷标记研究以及未发表的研究（通过计数抗微管蛋白抗体标记鉴定的有丝分裂纺锤体）所示，增殖反应迅速而广泛，涉及近端小管的许多剩余细胞。这种广泛的增殖能力被解释为反映了存活的上皮细胞通过去分化和增殖来适应邻近细胞的丧失的内在能力。粘附分子可能在肾上皮细胞迁移、增殖和分化的调节中起重要作用，细胞因子和趋化因子也是如此。更好地理解导致近端小管上皮细胞的去分化和增殖以及对这种修复功能重要的细胞-细胞和细胞-基质相互作用的所有特征，将导致设计用于促进人类恢复过程的治疗的新方法。
In contrast to the heart or brain, the kidney can completely recover from an ischemic or toxic insult that results in cell death. During recovery from ischemia/reperfusion injury, surviving tubular epithelial cells dedifferentiate and proliferate, eventually replacing the irreversibly injured tubular epithelial cells and restoring tubular integrity. Repair of the kidney parallels kidney organogenesis in the high rate of DNA synthesis and apoptosis and in patterns of gene expression. As has been shown by proliferating cell nuclear antigen and 5-bromo 2'-deoxyuridine labeling studies and, in unpublished studies, by counting mitotic spindles identified by labeling with antitubulin antibody, the proliferative response is rapid and extensive, involving many of the remaining cells of the proximal tubule. This extensive proliferative capacity is interpreted to reflect the intrinsic ability of the surviving epithelial cell to adapt to the loss of adjacent cells by dedifferentiating and proliferating. Adhesion molecules likely play important roles in the regulation of renal epithelial cell migration, proliferation, and differentiation, as do cytokines and chemokines. Better understanding of all of the characteristics resulting in dedifferentiation and proliferation of the proximal tubule epithelial cell and cell-cell and cell-matrix interactions important for this repair function will lead to novel approaches to therapies designed to facilitate the processes of recovery in humans.