Role of integrin and EGF in organogenesis of salivary gland

整合素和EGF在唾液腺器官发生中的作用

• 批准号: 13671949
• 负责人: KASHIMATA Masanori
• 金额: $ 1.41万
• 依托单位: ASAHI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671949/
• 关键词: EGF; EGFR; Erk; PLCγ1; PKC; PI3K; Branching; Morphogenesis; 唾液腺; 器官形成; ErbB; シグナル; Src; インテグリン; 上皮成長因子; チロシンキナーゼ; MAPK; P13K

Branching morphogenesis of fetal mouse submandibular glands (SMGs) partly depends on the EGF receptor that triggers at least three intracellular signaling pathways involving the ERK-1/2, PLCγ1, and PI3K. Western blotting revealed that PLCγ1 is present from E13 to E18 but drops of f precipitously to negligible levels on the day of birth and thereafter, and PI3K, PKB(Akt), and several PKC isozymes are expressed from E13 onward through adult life. Both PLCγ1 and PI3K are phosphorylated in response to EGF. Inhibition of PI3K by LY294002 inhibited EGF-stimulated branching, but inhibition of PLCgammal by U73122 had no effect. Western blotting showed that the concentrations of 8 PKC isozymes vary with age in the fetal and postnatal SMG. However, general inhibition of PKCs by Calphostin C or specific inhibition of PKCα or of PKCε by Go6976 or Ro-32-0432, respectively, increased EGF-stimulated branching. Calphostin C also increased EGF-stimulated phosphorylation of ERK-1/2. These findings indicate that signaling from the EGF receptor in the fetal mouse SMG varies with development and triggers stimulatory effects by means of ERK-112 and PI3K but inhibitory effects by means of PKC isozymes.

胎儿小鼠颌下腺 (SMG) 的分支形态发生部分取决于 EGF 受体，该受体触发至少三个细胞内信号通路：ERK-1/2、PLCγ1 和 PI3K。蛋白质印迹显示 PLCγ1 从 E13 到 E18 存在，但数量有所减少。 f 在出生当天及之后急剧降至可忽略不计的水平，并且 PI3K、PKB(Akt) 和几种PKC 同工酶从 E13 开始表达，直至成年。LY294002 对 PI3K 的抑制会抑制 EGF 刺激的分支，但 PLCγ1 和 PI3K 均会被磷酸化，但 U73122 对 PLCgammal 的抑制则没有效果。 8 PKC 同工酶在胎儿和出生后 SMG 中随年龄变化，但普遍受到抑制。 Calphostin C 的 PKC 或 Go6976 或 Ro-32-0432 对 PKCα 或 PKCε 的特异性抑制分别增加了 EGF 刺激的分支，这些结果表明来自 ERK-1/2 的信号传导。胎儿小鼠 SMG 中 EGF 受体的信号传导随发育而变化，并通过 ERK-112 和 PI3K 触发刺激作用，但抑制作用通过 PKC 同工酶发挥作用。

项目成果

Koyama, N., Kashimata, M., Sakagami, H., Gresik, E.W.: "EGF-stimulated signaling by means of PI3K, PLCγ1, and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular gland"Dev.Dyn.. 227. 216-226 (2003)

Koyama，N.，Kashimata，M.，Sakagami，H.，Gresik，E.W.：“通过 PI3K、PLCγ1 和 PKC 同工酶的 EGF 刺激信号调节胎儿小鼠颌下腺的分支形态发生”Dev.Dyn.. 227 216-226（2003）

Koyama, N., Kashimata, M., Sakashita, H., Sakagami, H., Gresik, E.: "EGF-stimulated signaling by mean of PI3K, PLCg1, and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular glands"Developmental Dynamics. 227. 216-226 (2003)

Koyama, N.、Kashimata, M.、Sakashita, H.、Sakagami, H.、Gresik, E.：“通过 PI3K、PLCg1 和 PKC 同工酶的 EGF 刺激信号调节胎儿小鼠颌下腺的分支形态发生”

柏俣正典, 小山典子, Gresik, E.W.: "胎仔マウス顎下腺に発現しているEGFシステム(EGFリガンドおよびErbB)の機能とシグナル伝達機構"日本唾液腺学会誌. (印刷中).

Masanori Kashiwamata、Noriko Koyama、Gresik、E.W.：“胚胎小鼠颌下腺中表达的 EGF 系统（EGF 配体和 ErbB）的功能和信号转导机制”日本唾液腺学会杂志（正在出版）。

Koyama, N., Gresik, E.W., Kashimata, M.: "EGF-stimulated signaling regulates branching morphogenesis of the fetal mouse submandibular glands"Journal of Japan Salivary Gland Sociey. (printing).

Koyama, N.、Gresik, E.W.、Kashimata, M.：“EGF 刺激信号调节胎儿小鼠下颌下腺的分支形态发生”日本唾液腺学会杂志。

Koyama, N., Kashimata, M., Gresik, E.: "EGF-stimulated signaling via P13K, PLCγl and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular gland"Developmental Dynamics. 227. 216-226 (2003)

Koyama，N.，Kashimata，M.，Gresik，E.：“通过 P13K、PLCγ1 和 PKC 同工酶的 EGF 刺激信号调节胎儿小鼠下颌下腺的分支形态发生”发育动力学 227. 216-226 (2003)。