Galectin-3 modulates ureteric bud branching in organ culture of the developing mouse kidney

Galectin-3 modulates ureteric bud branching in organ culture of the developing mouse kidney
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DOI:
10.1681/asn.v123515
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发表时间:
2001-03-01
影响因子:
13.6
通讯作者:
Woolf, AS
Woolf, AS
中科院分区:
医学1区
文献类型:
--
作者:
Bullock, SL;Johnson, TM;Woolf, AS

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Galectin-3是一种哺乳动物β-半乳糖苷特异性凝集素,具有细胞生长、粘附和肿瘤转化功能。在人类表达模式的基础上,提出半乳糖凝集素-3调节胎儿集合管生长。本文提供的证据表明,半乳糖凝集素3可以调节小鼠输尿管芽/集合管谱系的分支形态发生。使用免疫组织化学,半乳糖凝集素-3未检测到早期后肾,但上调后,在胎儿肾成熟时,蛋白质是突出的髓质集合管的基底域。此外,半乳糖凝集素-3胚胎第11天和第12天的整个后肾文化抑制输尿管芽分支,而半乳糖凝集素-1并没有扰乱形态发生,也没有半乳糖凝集素-3突变缺乏野生型高亲和力结合扩展寡糖。外源性半乳糖凝集素-3延缓了整个后肾外植体中肾间充质向肾单位的转化,但不影响脊髓在离体肾间充质中诱导肾单位。最后,添加半乳糖凝集素-3的阻断抗血清引起胚胎第12天后肾培养1周的发育上皮细胞扩张和变形。半乳糖凝集素-3蛋白在肾脏成熟过程中的上调,主要是在它可以介导细胞/基质相互作用的位点,似乎调节输尿管树的生长。
Galectin-3 is a mammalian beta -galactoside-specific lectin with functions in cell growth, adhesion, and neoplastic transformation. On the basis of expression patterns in humans, it is proposed that galectin-3 modulates fetal collecting duct growth. This article provides evidence that galectin3 can modulate branching morphogenesis of the mouse ureteric bud/ collecting duct lineage. With the use of immunohistochemistry, galectin-3 was not detected in early metanephrogenesis but was upregulated later in fetal kidney maturation when the protein was prominent in basal domains of medullary collecting ducts. Addition of galectin-3 to embryonic days 11 and 12 whole metanephric cultures inhibited ureteric bud branching, whereas galectin-1 did not perturb morphogenesis, nor did a galectin-3 mutant lacking wild-type high-affinity binding to extended oligosaccharides. Exogenous galectin-3 retarded conversion of renal mesenchyme to nephrons in whole metanephric explants but did not affect nephron induction by spinal cord in isolated renal mesenchymes. Finally, addition of a blocking antiserum to galectin-3 caused dilation and distortion of developing epithelia in embryonic day 12 metanephroi cultured for 1 wk. The upregulation of galectin-3 protein during kidney maturation, predominantly at sites where it could mediate cell/matrix interactions, seems to modulate growth of the ureteric tree.