The Role of Fgf Signaling on Epithelial Cell Differentiation in Mouse Vagina

Hirano, Yu; Suzuki, Kentaro; Iguchi, Taisen; Yamada, Gen; Miyagawa, Shinichi

doi:10.21873/invivo.11630

Cited by 5 publications

(1 citation statement)

References 43 publications

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“…In rodent reproductive organs such as the vagina and uterus, estrogen plays a regulatory role by binding to stromal expressed estrogen receptor α (ERα) [ 3 – 5 ]. Estrogen-induced stromal-secreted growth factors activate cell signal transduction through PI3K/Akt and mitogen-activated protein kinase (MAPK) signal cascade to promote epithelium proliferation [ 6 – 10 ]. Aberrant PI3K/Akt activation results in complex atypical hyperplasia and endometrioid carcinoma in the uterus [ 11 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation

Wan

Sun

et al. 2022

Cell Death Dis

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The mouse vaginal epithelium cyclically exhibits cell proliferation and differentiation in response to estrogen. Estrogen acts as an activator of mTOR signaling but its role in vaginal epithelial homeostasis is unknown. We analyzed reproductive tract-specific Rptor or Rictor conditional knockout mice to reveal the role of mTOR signaling in estrogen-dependent vaginal epithelial cell proliferation and differentiation. Loss of Rptor but not Rictor in the vagina resulted in an aberrant proliferation of epithelial cells and failure of keratinized differentiation. As gene expression analysis indicated, several estrogen-mediated genes, including Pgr and Ereg (EGF-like growth factor) were not induced by estrogen in Rptor cKO mouse vagina. Moreover, supplementation of EREG could activate the proliferation and survival of vaginal epithelial cells through YAP1 in the absence of Rptor. Thus, mTORC1 signaling integrates estrogen and growth factor signaling to mediate vaginal epithelial cell proliferation and differentiation, providing new insights into vaginal atrophy treatment for post-menopausal women.

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