Chiu Miliyun G, Johnson Tanya M, Woolf Adrian S, Dahm-Vicker Eugenia M, Long David A, Guay-Woodford Lisa, Hillman Katherine A, Bawumia Suleman, Venner Kerrie, Hughes R Colin, Poirier Francoise, Winyard Paul J D
Nephro-Urology Unit, UCL Institute of Child Health, 30 Guilford St., London WC1N 1EH, UK.
Am J Pathol. 2006 Dec;169(6):1925-38. doi: 10.2353/ajpath.2006.060245.
Several lines of evidence implicate the beta-galactoside-binding lectin galectin-3 in development and pathological processes in renal collecting ducts: galectin-3 is expressed in the ureteric bud/collecting duct lineage during nephrogenesis, modulates collecting duct growth/differentiation in vitro, and is expressed in human autosomal recessive polycystic kidney disease in cyst epithelia, almost all of which arise from collecting ducts. Moreover, exogenous galectin-3 restricts growth of cysts generated by Madin-Darby canine kidney collecting duct-derived cells in three-dimensional culture in collagen. Using the cpk mouse model of recessively inherited polycystic kidney disease, we observed widespread galectin-3 mRNA and protein in cyst epithelia. Exogenous galectin-3 reduced cyst formation in suspension culture, and mice-null mutant for galectin-3 had more extensive renal cysts in vivo. Galectin-3 was also detected for the first time in the centrosome/primary cilium, which has been implicated in diverse polycystic kidney disease. Cilia structure/number appeared normal in galectin-3-null mutants. Finally, paclitaxel, a therapy that retards polycystic kidney disease in cpk mice, increased extracellular galectin-3, in which the lectin could potentially interact with cilia. These data raise the possibility that galectin-3 may act as a natural brake on cystogenesis in cpk mice, perhaps via ciliary roles.
多项证据表明，β-半乳糖苷结合凝集素半乳糖凝集素-3参与肾集合管的发育和病理过程：在肾发生过程中，半乳糖凝集素-3在输尿管芽/集合管谱系中表达，在体外调节集合管的生长/分化，并且在人类常染色体隐性多囊肾病的囊肿上皮中表达，几乎所有囊肿都起源于集合管。此外，外源性半乳糖凝集素-3可限制马-达犬肾集合管衍生细胞在胶原蛋白三维培养中产生的囊肿生长。利用隐性遗传多囊肾病的cpk小鼠模型，我们观察到囊肿上皮中广泛存在半乳糖凝集素-3 mRNA和蛋白质。外源性半乳糖凝集素-3减少了悬浮培养中的囊肿形成，而半乳糖凝集素-3基因敲除小鼠在体内有更广泛的肾囊肿。在中心体/初级纤毛中也首次检测到半乳糖凝集素-3，而中心体/初级纤毛与多种多囊肾病有关。在半乳糖凝集素-3基因敲除突变体中，纤毛结构/数量似乎正常。最后，紫杉醇是一种可延缓cpk小鼠多囊肾病进展的疗法，它增加了细胞外半乳糖凝集素-3，该凝集素可能与纤毛相互作用。这些数据提示，半乳糖凝集素-3可能通过纤毛相关作用，作为cpk小鼠囊肿形成的天然制动器。
