Intrinsic epithelial cells repair the kidney after injury
Intrinsic epithelial cells repair the kidney after injury
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DOI：
10.1016/j.stem.2008.01.014
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发表时间：
2008-03-01
期刊：
影响因子：
23.9
通讯作者：
Bonventre, Joseph V.
中科院分区：
文献类型：
--
作者：
Humphreys, Benjamin D.;Valerius, M. Todd;Bonventre, Joseph V.
了解肾单位修复的机制对于设计治疗肾脏疾病的新治疗方法至关重要。即使是严重的损伤，肾脏也可以修复，但成体干细胞或祖细胞是否有助于损伤后的上皮更新以及再生细胞的细胞来源仍然存在争议。使用遗传命运作图技术，我们产生了转基因小鼠，其中94%-95%的肾小管上皮细胞，但没有间质细胞，用β-半乳糖苷酶（lacZ）或红色荧光蛋白（RFP）标记。缺血再灌注损伤（IRI）后两天，50.5%的外髓上皮细胞共表达Ki 67和RFP，表明损伤后存活的分化上皮细胞发生增殖性扩增。修复完成后，66.9%的上皮细胞已纳入BrdU，相比之下，只有3.5%的细胞在未受伤的肾脏。尽管有这种广泛的细胞增殖，但在修复后没有观察到任何细胞命运标志物的稀释。这些结果表明，存活的肾小管上皮细胞的再生是成年哺乳动物肾脏缺血性肾小管损伤后修复的主要机制。
Understanding the mechanisms of nephron repair is critical for the design of new therapeutic approaches to treat kidney disease. The kidney can repair after even a severe insult, but whether adult stem or progenitor cells contribute to epithelial renewal after injury and the cellular origin of regenerating cells remain controversial. Using genetic fate-mapping techniques, we generated transgenic mice in which 94%-95% of tubular epithelial cells, but no interstitial cells, were labeled with either beta-galactosidase (lacZ) or red fluorescent protein (RFP). Two days after ischemia-reperfusion injury (IRI), 50.5% of outer medullary epithelial cells coexpress Ki67 and RFP, indicating that differentiated epithelial cells that survived injury undergo proliferative expansion. After repair was complete, 66.9% of epithelial cells had incorporated BrdU, compared to only 3.5% of cells in the uninjured kidney. Despite this extensive cell proliferation, no dilution of either cell-fate marker was observed after repair. These results indicate that regeneration by surviving tubular epithelial cells is the predominant mechanism of repair after ischemic tubular injury in the adult mammalian kidney.