Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease
Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease
复制标题
DOI：
10.2353/ajpath.2006.060245
复制
发表时间：
2006-12-01
影响因子：
6
通讯作者：
Winyard, Paul J. D.
中科院分区：
文献类型：
--
作者：
Chiu, Miliyun G.;Johnson, Tanya M.;Winyard, Paul J. D.
多项证据表明，β-半乳糖苷结合凝集素 galectin-3 参与肾集合管的发育和病理过程：galectin-3 在肾发生期间的输尿管芽/集合管谱系中表达，在体外调节集合管生长/分化，并在人类常染色体隐性多囊肾囊肿上皮细胞中表达，几乎所有囊肿上皮都产生这种疾病。此外，外源性； galectin-3 限制 Madin-Darby 犬肾集合管衍生细胞在胶原蛋白三维培养中产生的囊肿的生长。使用隐性遗传性多囊肾病的 cpk 小鼠模型，我们观察到囊肿上皮细胞中广泛存在半乳糖凝集素 3 mRNA 和蛋白质。外源半乳糖凝集素 3 减少了悬浮培养中囊肿的形成，并且半乳糖凝集素 3 的小鼠磨机突变体在体内具有更广泛的肾囊肿。 Galectin-3 也首次在中心体/初级纤毛中检测到，该纤毛与多种多囊肾病有关。在半乳糖凝集素 3 缺失突变体中，纤毛结构/数量显得正常。最后，紫杉醇（一种延缓 cpk 小鼠多囊肾病的疗法）增加了细胞外半乳糖凝集素 3，其中凝集素可能与纤毛相互作用。这些数据提出了一种可能性，即半乳糖凝集素 3 可能通过纤毛作用，对 cpk 小鼠的囊肿发生发挥天然制动作用。
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-mill 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.