Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.
In Vivo. 2019 Sep-Oct;33(5):1499-1505. doi: 10.21873/invivo.11630.
BACKGROUND/AIM: The mouse vagina exhibits stratified squamous epithelium, which is comprised of multiple cell layers. We previously showed that erbB signaling, induced by epithelial estrogen receptor 1 (ESR1), is required for the initial differentiation of the epithelium. However, the downstream effector that mediates terminal differentiation in the apical layers remains elusive. The contribution of fibroblast growth factor (FGF) to vaginal epithelial cell differentiation was investigated.
Vaginas from wild-type or epithelium-specific Esr1 conditional knockout (cKO) mice were analyzed using immunohistochemistry and quantitative real-time RT-PCR.
Of the FGF ligands examined, Fgf22 mRNA was significantly induced following estrogen treatment. Furthermore, FGF downstream signaling, phosphorylated FRS2 and ERK1/2 were exclusively expressed in the apical layers of the vaginal epithelium. No changes in such expression were observed in the Esr1 cKO mice.
FGF-ERK/MAPK pathway may be a main inducer of terminal differentiation in the mouse vaginal epithelium.
背景/目的:小鼠阴道具有复层鳞状上皮,由多个细胞层组成。我们之前的研究表明,上皮雌激素受体 1(ESR1)诱导的 erbB 信号对于上皮的初始分化是必需的。然而,介导顶端细胞层终末分化的下游效应物仍不清楚。本研究旨在探讨成纤维细胞生长因子(FGF)对阴道上皮细胞分化的作用。
采用免疫组织化学和实时定量 RT-PCR 分析野生型或上皮特异性 Esr1 条件性敲除(cKO)小鼠的阴道。
在所研究的 FGF 配体中,Fgf22 mRNA 在雌激素处理后显著诱导。此外,FGF 下游信号转导,磷酸化 FRS2 和 ERK1/2 仅在阴道上皮的顶端层表达。在 Esr1 cKO 小鼠中未观察到这种表达的变化。
FGF-ERK/MAPK 通路可能是小鼠阴道上皮终末分化的主要诱导剂。