Expression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model
Activin A promotes the development of endometriotic lesions in a murine model of endometriosis, and the immunohistochemical localization of phosphorylated suppressor of mothers against decapentaplegic homolog 2/3 (pSMAD2/3) complex in endometriotic lesions has been reported. Activin may therefore be...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Japan Endocrine Society
2024-04-01
|
| Series: | Endocrine Journal |
| Subjects: | |
| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/4/71_EJ23-0486/_html/-char/en |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832591678536417280 |
|---|---|
| author | Yuri Kadota Takeshi Kato Kana Kasai Takako Kawakita Misaki Murayama Akari Shinya Hikari Sasada Sachiko Katayama Mari Nii Shota Yamamoto Hiroki Noguchi Kou Tamura Hidenori Aoki Miyu Taniguchi Tomotaka Nakagawa Takashi Kaji Masato Nishimura Riyo Kinouchi Kanako Yoshida Takeshi Iwasa |
| author_facet | Yuri Kadota Takeshi Kato Kana Kasai Takako Kawakita Misaki Murayama Akari Shinya Hikari Sasada Sachiko Katayama Mari Nii Shota Yamamoto Hiroki Noguchi Kou Tamura Hidenori Aoki Miyu Taniguchi Tomotaka Nakagawa Takashi Kaji Masato Nishimura Riyo Kinouchi Kanako Yoshida Takeshi Iwasa |
| author_sort | Yuri Kadota |
| collection | DOAJ |
| description | Activin A promotes the development of endometriotic lesions in a murine model of endometriosis, and the immunohistochemical localization of phosphorylated suppressor of mothers against decapentaplegic homolog 2/3 (pSMAD2/3) complex in endometriotic lesions has been reported. Activin may therefore be involved in the development and proliferation of endometriotic cells via the SMAD signaling pathway. However, few detailed reports exist on SMAD7 expression in endometriosis. The purpose of this study was to investigate the expression of pSMAD2/3 or pSMAD3 and SMAD7 in the orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model and the effect of activin A on pSMAD2/3 and SMAD7 expression. We established an endometriosis murine model via the intraperitoneal administration of endometrial tissue and blood from donor mice. Activin A was intraperitoneally administered to the activin group. We immunohistochemically evaluated orthotopic endometria, ovarian endometriotic tissues, and endometriotic lesions in the murine model followed by western blotting. We found that pSMAD3 and SMAD7 were expressed in ovarian endometriosis and orthotopic endometria from patients with and without endometriosis. In the murine model, endometriotic lesions expressed pSMAD2/3 and SMAD7 in the activin and control groups, and higher SMAD7 expression was found in the activin group. To the best of our knowledge, this study is the first to show that SMAD7 expression is upregulated in endometriosis. In conclusion, these results suggest that activin A activates the SMAD signaling pathway and promotes the development of endometriotic lesions, thus identifying SMAD7 as a potential therapeutic target for endometriosis. |
| format | Article |
| id | doaj-art-18d6b2144fed4703917247ed7535ca31 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-18d6b2144fed4703917247ed7535ca312025-01-22T06:37:03ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-04-0171439540110.1507/endocrj.EJ23-0486endocrjExpression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine modelYuri Kadota0Takeshi Kato1Kana Kasai2Takako Kawakita3Misaki Murayama4Akari Shinya5Hikari Sasada6Sachiko Katayama7Mari Nii8Shota Yamamoto9Hiroki Noguchi10Kou Tamura11Hidenori Aoki12Miyu Taniguchi13Tomotaka Nakagawa14Takashi Kaji15Masato Nishimura16Riyo Kinouchi17Kanako Yoshida18Takeshi Iwasa19Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanDepartment of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, JapanActivin A promotes the development of endometriotic lesions in a murine model of endometriosis, and the immunohistochemical localization of phosphorylated suppressor of mothers against decapentaplegic homolog 2/3 (pSMAD2/3) complex in endometriotic lesions has been reported. Activin may therefore be involved in the development and proliferation of endometriotic cells via the SMAD signaling pathway. However, few detailed reports exist on SMAD7 expression in endometriosis. The purpose of this study was to investigate the expression of pSMAD2/3 or pSMAD3 and SMAD7 in the orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model and the effect of activin A on pSMAD2/3 and SMAD7 expression. We established an endometriosis murine model via the intraperitoneal administration of endometrial tissue and blood from donor mice. Activin A was intraperitoneally administered to the activin group. We immunohistochemically evaluated orthotopic endometria, ovarian endometriotic tissues, and endometriotic lesions in the murine model followed by western blotting. We found that pSMAD3 and SMAD7 were expressed in ovarian endometriosis and orthotopic endometria from patients with and without endometriosis. In the murine model, endometriotic lesions expressed pSMAD2/3 and SMAD7 in the activin and control groups, and higher SMAD7 expression was found in the activin group. To the best of our knowledge, this study is the first to show that SMAD7 expression is upregulated in endometriosis. In conclusion, these results suggest that activin A activates the SMAD signaling pathway and promotes the development of endometriotic lesions, thus identifying SMAD7 as a potential therapeutic target for endometriosis.https://www.jstage.jst.go.jp/article/endocrj/71/4/71_EJ23-0486/_html/-char/enendometriosissuppressor of mothers against decapentaplegic (smad)suppressor of mothers against decapentaplegic 7 (smad7)activin a |
| spellingShingle | Yuri Kadota Takeshi Kato Kana Kasai Takako Kawakita Misaki Murayama Akari Shinya Hikari Sasada Sachiko Katayama Mari Nii Shota Yamamoto Hiroki Noguchi Kou Tamura Hidenori Aoki Miyu Taniguchi Tomotaka Nakagawa Takashi Kaji Masato Nishimura Riyo Kinouchi Kanako Yoshida Takeshi Iwasa Expression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model Endocrine Journal endometriosis suppressor of mothers against decapentaplegic (smad) suppressor of mothers against decapentaplegic 7 (smad7) activin a |
| title | Expression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model |
| title_full | Expression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model |
| title_fullStr | Expression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model |
| title_full_unstemmed | Expression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model |
| title_short | Expression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model |
| title_sort | expression of smads in orthotopic human endometrium ovarian endometriosis and endometriotic lesions in a murine model |
| topic | endometriosis suppressor of mothers against decapentaplegic (smad) suppressor of mothers against decapentaplegic 7 (smad7) activin a |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/4/71_EJ23-0486/_html/-char/en |
| work_keys_str_mv | AT yurikadota expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT takeshikato expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT kanakasai expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT takakokawakita expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT misakimurayama expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT akarishinya expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT hikarisasada expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT sachikokatayama expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT marinii expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT shotayamamoto expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT hirokinoguchi expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT koutamura expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT hidenoriaoki expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT miyutaniguchi expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT tomotakanakagawa expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT takashikaji expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT masatonishimura expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT riyokinouchi expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT kanakoyoshida expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel AT takeshiiwasa expressionofsmadsinorthotopichumanendometriumovarianendometriosisandendometrioticlesionsinamurinemodel |