LOCALIZATION OF PROLIFERATING CELL NUCLEAR ANTIGEN, VIMENTIN, C-FOS, AND CLUSTERIN IN THE POSTISCHEMIC KIDNEY - EVIDENCE FOR A HETEROGENOUS GENETIC RESPONSE AMONG NEPHRON SEGMENTS, AND A LARGE POOL OF MITOTICALLY ACTIVE AND DEDIFFERENTIATED CELLS
LOCALIZATION OF PROLIFERATING CELL NUCLEAR ANTIGEN, VIMENTIN, C-FOS, AND CLUSTERIN IN THE POSTISCHEMIC KIDNEY - EVIDENCE FOR A HETEROGENOUS GENETIC RESPONSE AMONG NEPHRON SEGMENTS, AND A LARGE POOL OF MITOTICALLY ACTIVE AND DEDIFFERENTIATED CELLS
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DOI：
10.1172/jci117214
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发表时间：
1994-05-01
影响因子：
15.9
通讯作者：
BONVENTRE, JV
中科院分区：
文献类型：
--
作者：
WITZGALL, R;BROWN, D;BONVENTRE, JV
导致缺血性急性肾功能衰竭后肾脏恢复的机制尚不清楚。为了探讨有丝分裂和去分化在这一修复过程中所起的作用，并确定肾单位段的遗传反应是否反映了损伤的易感性，我们检测了参与有丝分裂、分化和损伤的各种蛋白质的颞段和肾单位段的表达。增殖细胞核抗原是细胞周期中G(1)-S转换和有丝分裂的标志，主要在近端小管的S3段检测到，在缺血后2d表达最强。波形蛋白通常存在于间充质细胞中，而不存在于上皮细胞中，因此是分化状态的标志，在缺血后2-5d的S3节段显著表达。在S3节段髓外带细胞中，增殖细胞核抗原阳性的细胞也有波形蛋白阳性染色。Clusterin是细胞损伤的标志，主要在S3段和远端小管表达，每一段都有不同的染色模式。聚集素抗体染色的细胞均未见增殖细胞核抗原和波形蛋白抗体阳性。同样，增殖细胞核抗原或波形蛋白阳性细胞均未检测到聚集素的表达。因此，在S3节段，存在显著的缺血性损伤，存活的细胞表达标志，表明它们在缺血后阶段经历有丝分裂和去分化。C-Fos在S3节段有少量表达，但在缺血1h和3h，c-Fos主要表达在远端肾单位的核，特别是在粗大的升支。这些数据支持成熟的肾S3节段上皮细胞可以作为祖细胞的观点。
The mechanisms leading to the recovery of the kidney after ischemic acute renal failure are poorly understood. To explore the role played by mitogenesis and dedifferentiation in this repair process and to identify whether the genetic response of the nephron segments reflects the level of susceptibility to injury, the temporal and nephron segment expressions of various proteins implicated in mitogenesis, differentiation, and injury were determined. Proliferating cell nuclear antigen (PCNA), a marker for the G(1)-S transition in the cell cycle and hence mitogenesis, was detected primarily in the S3 segment of the proximal tubule, with maximal expression at 2 d postischemia. Vimentin, normally present in mesenchymal cells but not epithelial cells, and hence a marker for the state of differentiation, was prominently expressed in the S3 segment 2-5 d postischemia. In the S3 segments in the outer stripe of the medulla cells that stained positively for PCNA also stained positively for vimentin. Clusterin, a marker for cell injury, was expressed primarily in the S3 segment and in the distal tubule with distinct staining patterns in each segment. None of the cells that stained with clusterin antibodies were positively stained with PCNA or vimentin antibodies. Likewise, none of the PCNA or vimentin-positive cells expressed clusterin at detectable levels. Thus, in the S3 segment, where there is significant ischemic injury, surviving cells express markers indicating that they undergo mitogenesis and dedifferentiate in the postischemic period. While there is some expression of c-Fos in the S3 segment, c-Fos was expressed predominantly, at 1 and 3 h postischemia, in the nuclei of the distal nephron, particularly in the thick ascending limb. The data support the view that the mature renal S3 segment epithelial cell can be a progenitor cell.