Abbate M, Brown D, Bonventre J V
Renal Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Am J Physiol. 1999 Sep;277(3):F454-63. doi: 10.1152/ajprenal.1999.277.3.F454.
Recovery of the kidney from acute renal failure relies on a sequence of events including epithelial cell dedifferentiation and proliferation followed by differentiation and restoration of the functional integrity of the nephron. The factors responsible for, and the significance of, reversion to a less differentiated cell phenotype and its relationship to the proliferative response after ischemia are poorly understood. In an attempt to identify adhesion molecules that may be influential in the recovery process, the expression of neural cell adhesion molecule (NCAM) and markers of epithelial differentiation and proliferation were analyzed at various times after an ischemic insult. In maturing nephrons, NCAM is detectable by immunohistochemistry in renal vesicles, S-shaped bodies, and early tubules. There is minimal cellular NCAM expression in normal tubules of the adult kidney. In contrast, in postischemic kidneys, NCAM expression is abundant in S3 proximal tubule cells 5 days after reperfusion. As in developing tubules, NCAM is concentrated in basal and lateral aspects of cells that have no apical gp330 or dipeptidyl peptidase IV detectable on their brush border. The expression of NCAM is preceded by disassembly of the brush border and proliferation of surviving S3 cells, which is most prominent at 2 days postischemia. NCAM expression persists in some flattened and dedifferentiated cells for up to 7 wk after ischemia. Thus proximal tubule epithelial cells of the postischemic kidney express NCAM in a pattern that recapitulates the expression of NCAM in the developing kidney. Such reversion of phenotype extends at least back to the early stages of renal vesicle formation, and this reversion may represent a critical step in the reestablishment of a normal tubule. NCAM-matrix interactions may mediate the motogenic and mitogenic responses of the dedifferentiated epithelium that are critical to reestablishment of a functional proximal tubule.
肾脏从急性肾衰竭中恢复依赖于一系列事件，包括上皮细胞去分化和增殖，随后是分化以及肾单位功能完整性的恢复。目前对于导致细胞表型向低分化状态逆转的因素、其意义以及与缺血后增殖反应的关系了解甚少。为了确定可能在恢复过程中起作用的黏附分子，我们分析了缺血损伤后不同时间点神经细胞黏附分子（NCAM）的表达以及上皮分化和增殖的标志物。在成熟的肾单位中，通过免疫组织化学可在肾小囊、S形小体和早期肾小管中检测到NCAM。在成年肾脏的正常肾小管中，细胞NCAM表达极少。相比之下，在缺血后肾脏中，再灌注5天后S3近端小管细胞中NCAM表达丰富。与发育中的肾小管一样，NCAM集中在刷状缘未检测到顶端gp330或二肽基肽酶IV的细胞的基底和侧面。NCAM的表达之前是刷状缘的解体和存活的S3细胞的增殖，这在缺血后2天最为明显。缺血后NCAM表达在一些扁平的去分化细胞中持续长达7周。因此，缺血后肾脏的近端小管上皮细胞以一种重现发育中肾脏NCAM表达的模式表达NCAM。这种表型逆转至少可追溯到肾小囊形成的早期阶段，这种逆转可能代表了正常肾小管重建的关键步骤。NCAM与基质的相互作用可能介导去分化上皮细胞的促运动和促有丝分裂反应，这对于功能性近端小管的重建至关重要。
