Role of fibroblast growth factor receptor signaling in kidney development.
Role of fibroblast growth factor receptor signaling in kidney development.
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DOI：
10.1007/s00467-010-1747-z
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发表时间：
2011-09
影响因子：
3
通讯作者：
Bates, Carlton M.
中科院分区：
文献类型：
--
作者：
Bates, Carlton M.
关键词：
成纤维细胞生长因子受体(FGFRs)在发育中的肾脏中表达。一些早期的研究表明，外源性成纤维细胞生长因子(FGFs)影响后肾间充质(MM)和输尿管芽(UB)的生长和成熟。过度表达显性负性受体亚型的转基因小鼠会出现肾发育不全/严重不典型增生，证实了FGFRs在肾脏发育中的重要性。此外，在小鼠中，Fgf7、Fgf10和Fgfr2IIIb(结合Fgf7和Fgf10的异构体)的全局缺失导致小肾脏具有更少的集合管和肾单位。Fgfrl1是一种缺乏细胞内信号域的受体，它的缺失会导致严重的肾脏发育不良。MM有条件地靶向FGF8可阻断肾单位的形成。从UB中缺失FGFR2会导致严重的输尿管分支和间质间充质缺陷，尽管UB中的Frs2α(FGFRs的主要信号转接子)丢失只会导致轻微的肾脏发育不良。在多发性骨髓瘤中，FGFR1和FGFR2的缺失会导致肾发育不全，伴有多发性骨髓瘤形成和初始UB延长和分支的缺陷。多发性骨髓瘤中FGFR2的缺失导致许多肾脏和尿路异常，以及膀胱输尿管返流。因此，在发育的早期和后期，FGFR信号对于几乎所有肾脏谱系的模式都是至关重要的。
Fibroblast growth factor receptors (Fgfrs) are expressed throughout the developing kidney. Several early studies have shown that exogenous fibroblast growth factors (Fgfs) affect growth and maturation of the metanephric mesenchyme (MM) and ureteric bud (UB). Transgenic mice that overexpress a dominant negative receptor isoform develop renal aplasia/severe dysplasia, confirming the importance of Fgfrs in renal development. Furthermore, global deletion of Fgf7, Fgf10, and Fgfr2IIIb (isoform that binds Fgf7 and Fgf10) in mice leads to small kidneys with fewer collecting ducts and nephrons. Deletion of Fgfrl1, a receptor lacking intracellular signaling domains, causes severe renal dysgenesis. Conditional targeting of Fgf8 from the MM interrupts nephron formation. Deletion of Fgfr2 from the UB results in severe ureteric branching and stromal mesenchymal defects, although loss of Frs2α (major signaling adapter for Fgfrs) in the UB causes only mild renal hypoplasia. Deletion of both Fgfr1 and Fgfr2 in the MM results in renal aplasia with defects in MM formation and initial UB elongation and branching. Loss of Fgfr2 in the MM leads to many renal and urinary tract anomalies as well as vesicoureteral reflux. Thus, Fgfr signaling is critical for patterning of virtually all renal lineages at early and later stages of development.
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DOI：
10.1152/ajprenal.00382.2005
发表时间：
2006-08-01
影响因子：
4.2
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