Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity
Abstract Background The establishment of uterine receptivity is essential for embryo implantation initiation and involves a significant morphological transformation in the endometrial epithelial cells (EECs). The remodeling of junctional complexes and membrane-associated cytoskeleton is crucial for...
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Reproductive Biology and Endocrinology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12958-020-00689-7 |
| _version_ | 1819320527106342912 |
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| author | Jingjie Liang Kui Li Kaiyu Chen Junyong Liang Ti Qin Jiayi He Shuang Shi Qiang Tan Zhengguang Wang |
| author_facet | Jingjie Liang Kui Li Kaiyu Chen Junyong Liang Ti Qin Jiayi He Shuang Shi Qiang Tan Zhengguang Wang |
| author_sort | Jingjie Liang |
| collection | DOAJ |
| description | Abstract Background The establishment of uterine receptivity is essential for embryo implantation initiation and involves a significant morphological transformation in the endometrial epithelial cells (EECs). The remodeling of junctional complexes and membrane-associated cytoskeleton is crucial for epithelial transformation. However, little is known about how this process is regulated in EECs during the receptive phase. ARHGAP19 is a Rho GTPase-activating protein that participates in various cytoskeletal-related events, including epithelial morphogenesis. Here, we investigated the role of ARHGAP19 in endometrial epithelial transformation during the establishment of uterine receptivity. The upstream regulator of ARHGAP19 was also investigated. Methods ARHGAP19 expression was examined in mouse uteri during early pregnancy and in human EEC lines. The role of ARHGAP19 was investigated by manipulating its expression in EECs. The effect of ARHGAP19 on junctional proteins in EECs was examined by western blotting and immunofluorescence. The effect of ARHGAP19 on microvilli was examined by scanning electron microscopy. The upstream microRNA (miRNA) was predicted using online databases and validated by the dual-luciferase assay. The in vivo and in vitro effect of miRNA on endogenous ARHGAP19 was examined by uterine injection of miRNA agomirs and transfection of miRNA mimics or inhibitors. Results ARHGAP19 was upregulated in the receptive mouse uteri and human EECs. Overexpression of ARHGAP19 in non-receptive EECs downregulated the expression of junctional proteins and resulted in their redistribution. Meanwhile, upregulating ARHGAP19 reorganized the cytoskeletal structure of EECs, leading to a decline of microvilli and changes in cell configuration. These changes weakened epithelial cell polarity and promoted the transition of non-receptive EECs to a receptive phenotype. Besides, miR-192-5p, a miRNA that plays a key role in maintaining epithelial properties, was validated as an upstream regulator of ARHGAP19. Conclusion These results suggested that ARHGAP19 may contribute to the transition of EECs from a non-receptive to a receptive state by regulating the remodeling of junctional proteins and membrane-associated cytoskeleton. |
| first_indexed | 2024-12-24T11:20:59Z |
| format | Article |
| id | doaj.art-91e3364bc5984eab858dfbd38db46330 |
| institution | Directory Open Access Journal |
| issn | 1477-7827 |
| language | English |
| last_indexed | 2024-12-24T11:20:59Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Reproductive Biology and Endocrinology |
| spelling | doaj.art-91e3364bc5984eab858dfbd38db463302022-12-21T16:58:14ZengBMCReproductive Biology and Endocrinology1477-78272021-01-011911910.1186/s12958-020-00689-7Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivityJingjie Liang0Kui Li1Kaiyu Chen2Junyong Liang3Ti Qin4Jiayi He5Shuang Shi6Qiang Tan7Zhengguang Wang8College of Animal Science, Zhejiang UniversityZhejiang Animal Husbandry Techniques Extension StationCollege of Animal Science, Zhejiang UniversityCollege of Animal Science, Zhejiang UniversityCollege of Animal Science, Zhejiang UniversityCollege of Animal Science, Zhejiang UniversityCollege of Animal Science, Zhejiang UniversityCollege of Animal Science, Zhejiang UniversityCollege of Animal Science, Zhejiang UniversityAbstract Background The establishment of uterine receptivity is essential for embryo implantation initiation and involves a significant morphological transformation in the endometrial epithelial cells (EECs). The remodeling of junctional complexes and membrane-associated cytoskeleton is crucial for epithelial transformation. However, little is known about how this process is regulated in EECs during the receptive phase. ARHGAP19 is a Rho GTPase-activating protein that participates in various cytoskeletal-related events, including epithelial morphogenesis. Here, we investigated the role of ARHGAP19 in endometrial epithelial transformation during the establishment of uterine receptivity. The upstream regulator of ARHGAP19 was also investigated. Methods ARHGAP19 expression was examined in mouse uteri during early pregnancy and in human EEC lines. The role of ARHGAP19 was investigated by manipulating its expression in EECs. The effect of ARHGAP19 on junctional proteins in EECs was examined by western blotting and immunofluorescence. The effect of ARHGAP19 on microvilli was examined by scanning electron microscopy. The upstream microRNA (miRNA) was predicted using online databases and validated by the dual-luciferase assay. The in vivo and in vitro effect of miRNA on endogenous ARHGAP19 was examined by uterine injection of miRNA agomirs and transfection of miRNA mimics or inhibitors. Results ARHGAP19 was upregulated in the receptive mouse uteri and human EECs. Overexpression of ARHGAP19 in non-receptive EECs downregulated the expression of junctional proteins and resulted in their redistribution. Meanwhile, upregulating ARHGAP19 reorganized the cytoskeletal structure of EECs, leading to a decline of microvilli and changes in cell configuration. These changes weakened epithelial cell polarity and promoted the transition of non-receptive EECs to a receptive phenotype. Besides, miR-192-5p, a miRNA that plays a key role in maintaining epithelial properties, was validated as an upstream regulator of ARHGAP19. Conclusion These results suggested that ARHGAP19 may contribute to the transition of EECs from a non-receptive to a receptive state by regulating the remodeling of junctional proteins and membrane-associated cytoskeleton.https://doi.org/10.1186/s12958-020-00689-7ARHGAP19Uterine receptivityEpithelial transformationmiR-192-5p |
| spellingShingle | Jingjie Liang Kui Li Kaiyu Chen Junyong Liang Ti Qin Jiayi He Shuang Shi Qiang Tan Zhengguang Wang Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity Reproductive Biology and Endocrinology ARHGAP19 Uterine receptivity Epithelial transformation miR-192-5p |
| title | Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity |
| title_full | Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity |
| title_fullStr | Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity |
| title_full_unstemmed | Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity |
| title_short | Regulation of ARHGAP19 in the endometrial epithelium: a possible role in the establishment of uterine receptivity |
| title_sort | regulation of arhgap19 in the endometrial epithelium a possible role in the establishment of uterine receptivity |
| topic | ARHGAP19 Uterine receptivity Epithelial transformation miR-192-5p |
| url | https://doi.org/10.1186/s12958-020-00689-7 |
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