Renal Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2011 May 31;108(22):9226-31. doi: 10.1073/pnas.1100629108. Epub 2011 May 16.
Recently we have established that the kidney tubular epithelium is repaired by surviving epithelial cells. It is not known, however, whether a population of intratubular adult progenitor cells are responsible for this epithelial repair after acute kidney injury. In this study, we used an unbiased DNA analog-based approach that does not rely on candidate markers to track multiple rounds of cell division in vivo. In the proximal tubule, robust thymidine analog incorporation was observed postinjury. Cell division was stochastic and enriched among cells that were injured and dedifferentiated. There was no evidence for the presence of a population of specialized progenitors that repeatedly divide in response to injury. Instead, these results indicate that after injury, new epithelial cells arise from self-duplication of surviving cells, most of which are injured. Because the renal papilla contains DNA label-retaining cells and has been proposed as a stem cell niche, we examined the proliferative behavior of these putative progenitors after ischemia-reperfusion injury. Although label-retaining cells in the renal papilla diminished with time after ischemia-reperfusion injury, they neither proliferated nor migrated to the outer medulla or cortex. Thus, nonlethally injured cells repopulate the kidney epithelium after injury in the absence of any specialized progenitor cell population.
最近，我们已经证实肾脏管状上皮细胞是通过存活的上皮细胞进行修复的。然而，目前尚不清楚在急性肾损伤后，是否存在一群肾小管内的成体祖细胞负责这种上皮修复。在这项研究中，我们使用了一种无偏倚的基于 DNA 类似物的方法，该方法不依赖于候选标志物来追踪体内多轮细胞分裂。在近端小管中，损伤后观察到强烈的胸腺嘧啶类似物掺入。细胞分裂是随机的，并且在受伤和去分化的细胞中富集。没有证据表明存在一群专门的祖细胞，它们会反复分裂以响应损伤。相反，这些结果表明，损伤后，新的上皮细胞是由存活细胞的自我复制产生的，其中大多数细胞都受到了损伤。由于肾乳头含有 DNA 标记保留细胞，并被提议作为干细胞龛，我们在缺血再灌注损伤后检查了这些假定祖细胞的增殖行为。尽管缺血再灌注损伤后肾乳头中的标记保留细胞随时间减少，但它们既没有增殖，也没有迁移到外髓质或皮质。因此，在没有任何专门的祖细胞群体的情况下，非致死性损伤细胞在损伤后重新填充肾脏上皮。
