Epithelial Bmp (Bone morphogenetic protein) signaling for bulbourethral gland development: a mouse model for congenital cystic dilation.
Epithelial Bmp (Bone morphogenetic protein) signaling for bulbourethral gland development: a mouse model for congenital cystic dilation.
复制标题
尿道球腺发育的上皮 Bmp（骨形态发生蛋白）信号传导：先天性囊性扩张的小鼠模型。
DOI：
10.1111/j.1741-4520.2011.00318.x
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发表时间：
2011
影响因子：
1.3
通讯作者：
Yamada,Gen
中科院分区：
文献类型：
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作者：
Omori,Akiko;Harada,Masayo;Ohta,Sho;Villacorte,Mylah;Sugimura,Yoshiki;Shiraishi,Taizou;Suzuki,Kentaro;Nakagata,Naomi;Ito,Takaaki;Yamada,Gen
尿道球腺（BUG）是男性特有的器官，可分泌部分精液。由于BUG位于盆底深部，其发育过程尚不清楚。骨形态发生蛋白 (Bmp) 信号传导在多种器官中发挥着关键作用。然而，Bmp 信号传导在 BUG 发展中的功能仍不清楚。本研究旨在阐明 Bmp 信号在 BUG 发展中的作用。我们观察到 BUG 上皮发育过程中 Bmp 信号下游分子磷酸化 (p) SMAD1/5/8 的显着核积累。这些结果表明 Bmp 信号传导有助于 BUG 的发展。 Bmp 受体 1a (Bmpr1a) 被认为是某些器官发生中主要的 1 型信号转导器。为了分析BUG发展的Bmp信号传导功能，我们利用他莫昔芬诱导的Cre重组酶系统检查了上皮细胞特异性Bmpr1agene条件突变小鼠。我们在Bmpr1a条件敲除小鼠中观察到BUG的囊性扩张和上皮增生。突变囊性BUG标本也显示出炎性病变。这些 BUG 异常类似于人类先天性综合症中观察到的一些 BUG 畸形。目前的研究表明，Bmp 信号传导在 BUG 发育和稳态中具有重要作用。这将是第一份报告，表明 BUG 上皮细胞中 Bmpr1 基因的突变表现出影响 BUG 导管的人类先天性综合征的一些异常。
The bulbourethral gland (BUG) is a male‐specific organ, which secretes part of the semen fluid. As the BUG is located in the deep pelvic floor, its developmental process is still unclear. Bone morphogenetic protein (Bmp) signaling plays pivotal roles in various organs. However, the function of Bmp signaling for BUG development is still unclear. The present study aimed to elucidate the role of Bmp signaling in the development of the BUG. We observed the prominent nuclear accumulation of phosphorylated (p) SMAD1/5/8, the downstream molecules of Bmp signaling, during BUG epithelial development. These results suggest that Bmp signaling contributes to BUG development. Bmp receptor1a (Bmpr1a) is known as the major type 1 signal transducer in some organogeneses. To analyze the Bmp signaling function for BUG development, we examined epithelial cell‐specificBmpr1agene conditional mutant mice utilizing the tamoxifen‐inducible Cre recombinase system. We observed cystic dilation and epithelial hyperplasia of the BUG in theBmpr1aconditional knockout mice. The mutant cystic BUG specimens also showed inflammatory lesions. These BUG abnormalities resembled some of the BUG malformations observed in human congenital syndromes. The current study suggests that Bmp signaling possesses an essential role in BUG development and homeostasis. This would be the first report showing that the mutation of theBmpr1agene in the BUG epithelia phenocopied some abnormalities of human congenital syndromes affecting the BUG duct.