雄激素/Wnt/β-catenin信号轴增强小鼠勃起组织海绵体细胞增殖。

IF 1.3 4区 医学 Q3 PEDIATRICS
Congenital Anomalies Pub Date : 2022-05-01 Epub Date: 2022-03-29 DOI:10.1111/cga.12465
Mizuki Kajimoto, Kentaro Suzuki, Yuko Ueda, Kota Fujimoto, Toru Takeo, Naomi Nakagata, Taiju Hyuga, Kyoichi Isono, Gen Yamada
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引用次数: 4

摘要

小鼠阴茎勃起组织包括海绵体(CC),由血管、平滑肌和结缔组织组成,性别差异明显。众所周知,雄激素是两性二形器官发生所必需的。然而,在小鼠CC发育过程中雄激素信号的特征尚不清楚。目前还不清楚雄激素驱动的下游因子是如何参与这一过程的。在本研究中,我们基于组织学分析、雄激素受体(AR)表达的动态和细胞增殖的调节分析了两性二态CC形成的开始。值得注意的是,我们发现dickkopf相关蛋白2 (Dkk2),一种β-catenin信号传导抑制剂,与男性相比,在女性CC中主要表达。此外,雄激素的管理导致β-catenin信号的激活。我们发现Sox9基因是软骨细胞的重要标记之一,在发育中的CC中特异性表达,因此我们使用CC特异性的Sox9 CreERT2 β-catenin条件突变小鼠。这种突变小鼠表现出细胞增殖缺陷。此外,在CC中引入活化形式的β-catenin突变(Wnt/β-catenin信号功能突变的获得)诱导细胞增殖增强。总之,我们发现雄激素- wnt /β-catenin信号依赖性细胞增殖是两性二态CC形成的必要条件。这些发现为理解性分化过程中雄激素依赖性细胞增殖的发育机制开辟了新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Androgen/Wnt/β-catenin signal axis augments cell proliferation of the mouse erectile tissue, corpus cavernosum.

The murine penile erectile tissues including corpus cavernosum (CC) are composed of blood vessels, smooth muscle, and connective tissue, showing marked sexual differences. It has been known that the androgens are required for sexually dimorphic organogenesis. It is however unknown about the features of androgen signaling during mouse CC development. It is also unclear how androgen-driven downstream factors are involved such processes. In the current study, we analyzed the onset of sexually dimorphic CC formation based on histological analyses, the dynamics of androgen receptor (AR) expression, and regulation of cell proliferation. Of note, we identified Dickkopf-related protein 2 (Dkk2), an inhibitor of β-catenin signaling, was predominantly expressed in female CC compared with male. Furthermore, administration of androgens resulted in activation of β-catenin signaling. We have found the Sox9 gene, one of the essential markers for chondrocyte, was specifically expressed in the developing CC. Hence, we utilized CC-specific, Sox9 CreERT2 , β-catenin conditional mutant mice. Such mutant mice showed defective cell proliferation. Furthermore, introduction of activated form of β-catenin mutation (gain of function mutation for Wnt/β-catenin signaling) in CC induced augmented cell proliferation. Altogether, we revealed androgen-Wnt/β-catenin signal dependent cell proliferation was essential for sexually dimorphic CC formation. These findings open new avenues for understanding developmental mechanisms of androgen-dependent cell proliferation during sexual differentiation.

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来源期刊
Congenital Anomalies
Congenital Anomalies PEDIATRICS-
自引率
0.00%
发文量
49
审稿时长
>12 weeks
期刊介绍: Congenital Anomalies is the official English language journal of the Japanese Teratology Society, and publishes original articles in laboratory as well as clinical research in all areas of abnormal development and related fields, from all over the world. Although contributions by members of the teratology societies affiliated with The International Federation of Teratology Societies are given priority, contributions from non-members are welcomed.
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