Mechanisms of Parathyroid Hormone Receptor Signaling in Mouse Salivary Gland Development.

小鼠唾液腺发育中甲状旁腺激素受体信号传导的机制。

• 批准号: 16591994
• 负责人: AIKAWA Tomonao
• 金额: $ 2.3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591994/
• 关键词: salivary gland development; parathyroid hormone receptor; branching; protein kinase C (PKC); protein kinase A (PKA)

This study has focused on clarifying the roles of Parathyroid hormone receptor (PTHR) signaling in salivary gland development.Expression of PTHR and its ligand, Parathyroid hormone related peptide (PTHrP), in developing mouse salivary gland, was examined by qualitative PCR, in situ hybridization and immunohistochemistry. Expression level of PTHrP was peaked at E13.5,and then gradually decreased in developing mouse submandibular gland. On the other hand, expression level of PTHR peaked at E14.5 to E15.5, and then gradually decreased. PTHrP and PTHR were dominantly expressed in epithelial cells rather than mesenchymal cells. Intracellular signaling of PTHR utilizes 2 G-protein pathways, Gs and Gq. Both Gs and Gq subunit were expressed in epithelial cells of salivary gland.To assess the roles of PTHR signaling in salivary gland development, we have analyzed the salivary glands of PTHR-null mice. Submandibular glands in PTHR-null mice developed normally during E12.5 to E15.5,and then faile … More d to develop buds, as compared to those of litter mate wild-type mice. Furthermore, BrdU incorporation into cellular nuclei was decreased in salivary gland epithelial cells of PTHR-null mice at E15.0, compared to that of wild type mice, when assessed by BrdU staining. These findings suggest that inhibited cellular proliferation of salivary gland epithelial cells resulted in reduced bud development.To examine which intracellular signaling pathway, Gs-cascade or Gq-cascade, stimulate budding development of salivary gland, we have stimulated those secondary messenger in salivary glands explants culture by those specific stimulating analogs. Stimulation of Gq-phospholipase C stimulated bud development of salivary glands in a dowse dependent manner. On the other hand, stimulation of Gs-adenylcyclase-cAMP reduced bud development and stimulated duct development. These findings suggest that PTHR signaling stimulate bud development of salivary glands via Gq-PKC cascade.In salivary gland development, receptor tyrosine kinase receptor signaling, i.e. EGF, FGF and HGF, activate PKC signaling and stimulate bud development. However, there was no effect of PTHR ligands on EGF or FGF induced-bud development, suggesting that PTHR use distinct PKC-signaling pathway from receptor tyrosine kinase signaling. Less

本研究旨在阐明甲状旁腺激素受体(PTHR)信号转导通路在唾液腺发育中的作用。采用定性PCR、原位杂交和免疫组织化学方法检测PTHR及其配体甲状旁腺激素相关肽(PTHrP)在小鼠唾液腺发育过程中的表达。在发育中的小鼠颌下腺中，PTHrP的表达水平在胚胎13.5时达到高峰，然后逐渐下降。另一方面，PTHR的表达水平在胚胎14.5~15.5达到高峰，然后逐渐下降。PTHrP和PTHR主要在上皮细胞表达，间充质细胞不表达。PTHR的细胞内信号转导途径有两条：Gs和Gq。在涎腺上皮细胞中表达Gs和Gq亚基。为了评估PTHR信号在唾液腺发育中的作用，我们分析了PTHR缺失小鼠的唾液腺。Pthr基因缺失小鼠的颌下腺在E12.5到E15.5期间发育正常，然后是File…与野生型小鼠相比，发育芽所需的d更多。此外，通过BrdU染色，与野生型小鼠相比，PTHR基因缺失小鼠E15.0的唾液腺上皮细胞中BrdU掺入细胞核中的BrdU减少。这些发现表明，抑制唾液腺上皮细胞的增殖导致芽发育减少。为了研究哪一种细胞内信号通路，Gs级联或GQ级联，刺激唾液腺萌发，我们用这些特定的刺激类似物刺激唾液腺外植体中的次级信使。刺激GQ-磷脂酶C以一种脉冲依赖的方式刺激唾液腺的芽发育。另一方面，Gs-腺苷环化酶-cAMP的刺激抑制了芽的发育，刺激了导管的发育。这些结果表明，PTHR信号通过GQ-PKC通路刺激唾液腺的芽发育，在唾液腺发育中，受体酪氨酸激酶受体信号，即EGF、FGF和HGF，激活PKC信号，刺激芽的发育。然而，PTHR配体对EGF或FGF诱导的芽发育没有影响，这表明PTHR使用与受体酪氨酸激酶信号不同的PKC信号通路。较少

项目成果

マウス顎下腺発達における副甲状腺ホルモン受容体シグナルの役割に関する研究

甲状旁腺激素受体信号在小鼠颌下腺发育中的作用研究

• 发表时间: 2005
• 期刊: 大阪大学歯学雑誌 49・2
• 作者: Nishida M;Yasuda S;Murakami K;Yamamura I;Nagata Y;Iizuka T.;朴 一根
• 通讯作者: 朴 一根

Roles of Parathyroid hormone Receptor Signaling in Mouse Salivary Gland Development

甲状旁腺激素受体信号在小鼠唾液腺发育中的作用

• 发表时间: 2005
• 期刊: The Journal of Osaka University Dental Society 49(2)
• 作者: Yanagita M.;Okuda;T.;Endo;S.;Tanaka;M.;Takahashi;K.;Sugiyama;F.;Kunita;S.;Takahashi;S.;Fukatsu;A.;Yanagisawa M.;Kita;T.;Sakurai T;IL KUEN PARK
• 通讯作者: IL KUEN PARK