REDISTRIBUTION AND DYSFUNCTION OF INTEGRINS IN CULTURED RENAL EPITHELIAL-CELLS EXPOSED TO OXIDATIVE STRESS
REDISTRIBUTION AND DYSFUNCTION OF INTEGRINS IN CULTURED RENAL EPITHELIAL-CELLS EXPOSED TO OXIDATIVE STRESS
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DOI：
10.1152/ajprenal.1993.264.1.f149
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发表时间：
1993-01-01
影响因子：
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通讯作者：
GOLIGORSKY, MS
中科院分区：
文献类型：
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作者：
GAILIT, J;COLFLESH, D;GOLIGORSKY, MS
肾小管上皮细胞脱落引起的肾小管梗阻是急性肾功能衰竭少尿的主要原因。从急性肾小管坏死患者的尿液中可以回收到活的肾小管细胞，这表明细胞与基底膜的粘附可能存在缺陷。为了研究这一过程中的上皮细胞脱屑在体外，我们研究了非致死性氧化应激的灵长类动物肾上皮细胞系BS-C-1的整合素粘附受体的影响。细胞粘附特性的形态学和功能研究包括以下内容：干涉反射显微镜、活体共聚焦显微镜和免疫细胞化学、整合素受体丰度的流式细胞术分析和细胞-基质附着测定。通过荧光激活细胞分选（FACS）分析，在细胞表面检测到高水平的整合素亚基α 3、α（v）和β 1，以及较低水平的α 1、α 2、α 4、α 5、α 6和β 3。BS-C-1细胞暴露于非致死性氧化应激导致局灶性接触中断，塔林从基底细胞表面消失，并导致整合素α 3亚基从主要的基底位置重新分布到顶端细胞表面。如在定量细胞粘附测定中所测量的，氧化应激降低了BS-C-1细胞与IV型胶原、层粘连蛋白、纤连蛋白和玻连蛋白的粘附。粘附缺陷与细胞表面α 3-、α 4-或α（v）-整联蛋白亚基的丢失无关。我们的结论是，非致死性氧化应激削弱上皮细胞附着细胞外基质破坏局灶性接触，通过改变整合素受体的生理分布，并通过损害受体功能。
Tubular obstruction by detached renal tubular epithelial cells is a major cause of oliguria in acute renal failure. Viable renal tubular cells can be recovered from urine of patients with acute tubular necrosis, suggesting a possible defect in cell adhesion to the basement membrane. To study this process of epithelial cell desquamation in vitro, we investigated the effect of nonlethal oxidative stress on the integrin adhesion receptors of the primate kidney epithelial cell line BS-C-1. Morphological and functional studies of cell adhesion properties included the following: interference reflection microscopy, intravital confocal microscopy and immunocytochemistry, flow cytometric analysis of integrin receptor abundance, and cell-matrix attachment assay. High levels of the integrin subunits alpha3, alpha(v), and beta1 were detected on the cell surface by fluorescence-activated cell sorting (FACS) analysis, as well as lower levels of alpha1, alpha2, alpha4, alpha5, alpha6, and beta3. Exposure of BS-C-1 cells to nonlethal oxidative stress resulted in the disruption of focal contacts, disappearance of talin from the basal cell surface, and in the redistribution of integrin alpha3-subunits from predominantly basal location to the apical cell surface. As measured in a quantitative cell attachment assay, oxidative stress decreased BS-C-1 cell adhesion to type IV collagen, laminin, fibronectin, and vitronectin. Defective adhesion was not associated with a loss of alpha3-, alpha4-, or alpha(v)-integrin subunits from the cell surface. We conclude that nonlethal oxidative stress weakens epithelial cell attachment to the extracellular matrix by disrupting focal contacts, by altering physiological distribution of integrin receptors, and by impairing receptor function.