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干细胞标志物 TRA-1-60 在胎儿和成人肾脏中表达,并在上皮间质疾病中上调。

Stem cell marker TRA-1-60 is expressed in foetal and adult kidney and upregulated in tubulo-interstitial disease.

机构信息

Infection, Inflammation and Immunity Division, School of Medicine, University of Southampton, Southampton, UK.

出版信息

Histochem Cell Biol. 2010 Oct;134(4):355-69. doi: 10.1007/s00418-010-0741-7. Epub 2010 Sep 19.

Abstract

The kidney has an intrinsic ability to repair itself when injured. Epithelial cells of distal tubules may participate in regeneration. Stem cell marker, TRA-1-60 is linked to pluripotency in human embryonic stem cells and is lost upon differentiation. TRA-1-60 expression was mapped and quantified in serial sections of human foetal, adult and diseased kidneys. In 8- to 10-week human foetal kidney, the epitope was abundantly expressed on ureteric bud and structures derived therefrom including collecting duct epithelium. In adult kidney inner medulla/papilla, comparisons with reactivity to epithelial membrane antigen, aquaporin-2 and Tamm-Horsfall protein, confirmed extensive expression of TRA-1-60 in cells lining collecting ducts and thin limb of the loop of Henle, which may be significant since the papillae were proposed to harbour slow cycling cells involved in kidney homeostasis and repair. In the outer medulla and cortex there was rare, sporadic expression in tubular cells of the collecting ducts and nephron, with positive cells confined to the thin limb and thick ascending limb and distal convoluted tubules. Remarkably, in cortex displaying tubulo-interstitial injury, there was a dramatic increase in number of TRA-1-60 expressing individual cells and in small groups of cells in distal tubules. Dual staining showed that TRA-1-60 positive cells co-expressed Pax-2 and Ki-67, markers of tubular regeneration. Given the localization in foetal kidney and the distribution patterns in adults, it is tempting to speculate that TRA-1-60 may identify a population of cells contributing to repair of distal tubules in adult kidney.

摘要

肾脏具有自我修复的内在能力。远端肾小管的上皮细胞可能参与再生。干细胞标志物 TRA-1-60 与人类胚胎干细胞的多能性有关,在分化后会丢失。TRA-1-60 表达在人类胎儿、成人和患病肾脏的连续切片中进行了定位和定量。在 8 至 10 周的人类胎儿肾脏中,该抗原在输尿管芽及其衍生结构(包括集合管上皮)上大量表达。在成人肾脏的内髓质/乳头中,与上皮膜抗原、水通道蛋白-2 和 Tamm-Horsfall 蛋白的反应性进行比较,证实了 TRA-1-60 在集合管和 Henle 袢的薄升支衬里细胞中的广泛表达,这可能是重要的,因为乳头被认为含有参与肾脏稳态和修复的缓慢循环细胞。在外髓质和皮质中,在集合管和肾单位的管状细胞中仅有罕见的散在表达,阳性细胞仅限于薄升支和厚升支以及远端卷曲小管。值得注意的是,在显示肾小管间质损伤的皮质中,表达 TRA-1-60 的单个细胞和小群细胞数量显著增加。双重染色显示,TRA-1-60 阳性细胞共同表达 Pax-2 和 Ki-67,这是管状再生的标志物。鉴于在胎儿肾脏中的定位和在成人中的分布模式,人们不禁推测 TRA-1-60 可能识别出参与成人肾脏远端小管修复的细胞群体。

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