mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation
Abstract 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 kno...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-10-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05293-8 |
| _version_ | 1798029969454006272 |
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| author | Shuo Wan Yadong Sun Jiamin Fu Hongrui Song Zhiqiang Xiao Quanli Yang Sanfeng Wang Gongwang Yu Peiran Feng Wenkai Lv Liang Luo Zerong Guan Feng Liu Qinghua Zhou Zhinan Yin Meixiang Yang |
| author_facet | Shuo Wan Yadong Sun Jiamin Fu Hongrui Song Zhiqiang Xiao Quanli Yang Sanfeng Wang Gongwang Yu Peiran Feng Wenkai Lv Liang Luo Zerong Guan Feng Liu Qinghua Zhou Zhinan Yin Meixiang Yang |
| author_sort | Shuo Wan |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T19:32:46Z |
| format | Article |
| id | doaj.art-4cac7673fd9949eb9a20103e2f44a646 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T19:32:46Z |
| publishDate | 2022-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-4cac7673fd9949eb9a20103e2f44a6462022-12-22T04:06:56ZengNature Publishing GroupCell Death and Disease2041-48892022-10-01131011410.1038/s41419-022-05293-8mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiationShuo Wan0Yadong Sun1Jiamin Fu2Hongrui Song3Zhiqiang Xiao4Quanli Yang5Sanfeng Wang6Gongwang Yu7Peiran Feng8Wenkai Lv9Liang Luo10Zerong Guan11Feng Liu12Qinghua Zhou13Zhinan Yin14Meixiang Yang15The First Affiliated Hospital, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityGuangdong Women and Children HospitalDepartment of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityThe First Affiliated Hospital, Jinan UniversityGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan UniversityThe First Affiliated Hospital, Jinan UniversityAbstract 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.https://doi.org/10.1038/s41419-022-05293-8 |
| spellingShingle | Shuo Wan Yadong Sun Jiamin Fu Hongrui Song Zhiqiang Xiao Quanli Yang Sanfeng Wang Gongwang Yu Peiran Feng Wenkai Lv Liang Luo Zerong Guan Feng Liu Qinghua Zhou Zhinan Yin Meixiang Yang mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation Cell Death and Disease |
| title | mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation |
| title_full | mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation |
| title_fullStr | mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation |
| title_full_unstemmed | mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation |
| title_short | mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation |
| title_sort | mtorc1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation |
| url | https://doi.org/10.1038/s41419-022-05293-8 |
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