Notch2 Regulates the Function of Bovine Follicular Granulosa Cells via the Wnt2/β-Catenin Signaling Pathway
Ovarian follicular GCs are strongly implicated in the growth, development, and atresia of ovarian follicles. The Wnt/β-catenin and Notch signaling pathways participate in GC proliferation, differentiation, apoptosis, and steroid hormone production during follicular development. However, the crosstal...
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MDPI AG
2024-03-01
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author | Wenqing Dang Yongping Ren Qingqing Chen Min He Ermias Kebreab Dong Wang Lihua Lyu |
author_facet | Wenqing Dang Yongping Ren Qingqing Chen Min He Ermias Kebreab Dong Wang Lihua Lyu |
author_sort | Wenqing Dang |
collection | DOAJ |
description | Ovarian follicular GCs are strongly implicated in the growth, development, and atresia of ovarian follicles. The Wnt/β-catenin and Notch signaling pathways participate in GC proliferation, differentiation, apoptosis, and steroid hormone production during follicular development. However, the crosstalk between Wnt and Notch signaling in GCs remains unclear. This study investigated this crosstalk and the roles of these pathways in apoptosis, cell cycle progression, cell proliferation, and steroid hormone secretion in bovine follicular GCs. The interaction between β-catenin and Notch2 in GCs was assessed by overexpressing <i>CTNNB1</i>, which encodes β-catenin. The results showed that inhibiting the Notch pathway by Notch2 silencing in GCs arrested the cell cycle, promoted apoptosis, reduced progesterone (P4) production, and inhibited the Wnt2-mediated Wnt/β-catenin pathway in GCs. IWR-1 inhibited Wnt2/β-catenin and Notch signaling, reduced GC proliferation, stimulated apoptosis, induced G1 cell cycle arrest, and reduced P4 production. <i>CTNNB1</i> overexpression had the opposite effect and increased 17β-estradiol (E2) production and Notch2 protein expression. Co-immunoprecipitation assays revealed that Notch2 interacted with β-catenin. These results elucidate the crosstalk between the Wnt/β-catenin and Notch pathways and the role of these pathways in bovine follicular GC development. |
first_indexed | 2024-04-24T10:50:53Z |
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id | doaj.art-4bfe5ceb42b646f5981b91adc241c5af |
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issn | 2076-2615 |
language | English |
last_indexed | 2024-04-24T10:50:53Z |
publishDate | 2024-03-01 |
publisher | MDPI AG |
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series | Animals |
spelling | doaj.art-4bfe5ceb42b646f5981b91adc241c5af2024-04-12T13:14:05ZengMDPI AGAnimals2076-26152024-03-01147100110.3390/ani14071001Notch2 Regulates the Function of Bovine Follicular Granulosa Cells via the Wnt2/β-Catenin Signaling PathwayWenqing Dang0Yongping Ren1Qingqing Chen2Min He3Ermias Kebreab4Dong Wang5Lihua Lyu6College of Animal Science, Shanxi Agricultural University, Taigu, Jinzhong 030801, ChinaCollege of Animal Science, Shanxi Agricultural University, Taigu, Jinzhong 030801, ChinaCollege of Animal Science, Shanxi Agricultural University, Taigu, Jinzhong 030801, ChinaCollege of Animal Science, Shanxi Agricultural University, Taigu, Jinzhong 030801, ChinaCollege of Agricultural and Environmental Sciences, University of California, Davis, CA 95616, USAInstitute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaCollege of Animal Science, Shanxi Agricultural University, Taigu, Jinzhong 030801, ChinaOvarian follicular GCs are strongly implicated in the growth, development, and atresia of ovarian follicles. The Wnt/β-catenin and Notch signaling pathways participate in GC proliferation, differentiation, apoptosis, and steroid hormone production during follicular development. However, the crosstalk between Wnt and Notch signaling in GCs remains unclear. This study investigated this crosstalk and the roles of these pathways in apoptosis, cell cycle progression, cell proliferation, and steroid hormone secretion in bovine follicular GCs. The interaction between β-catenin and Notch2 in GCs was assessed by overexpressing <i>CTNNB1</i>, which encodes β-catenin. The results showed that inhibiting the Notch pathway by Notch2 silencing in GCs arrested the cell cycle, promoted apoptosis, reduced progesterone (P4) production, and inhibited the Wnt2-mediated Wnt/β-catenin pathway in GCs. IWR-1 inhibited Wnt2/β-catenin and Notch signaling, reduced GC proliferation, stimulated apoptosis, induced G1 cell cycle arrest, and reduced P4 production. <i>CTNNB1</i> overexpression had the opposite effect and increased 17β-estradiol (E2) production and Notch2 protein expression. Co-immunoprecipitation assays revealed that Notch2 interacted with β-catenin. These results elucidate the crosstalk between the Wnt/β-catenin and Notch pathways and the role of these pathways in bovine follicular GC development.https://www.mdpi.com/2076-2615/14/7/1001Notch2Wnt2/β-cateninbovinefollicular granulosa cellsinteraction |
spellingShingle | Wenqing Dang Yongping Ren Qingqing Chen Min He Ermias Kebreab Dong Wang Lihua Lyu Notch2 Regulates the Function of Bovine Follicular Granulosa Cells via the Wnt2/β-Catenin Signaling Pathway Animals Notch2 Wnt2/β-catenin bovine follicular granulosa cells interaction |
title | Notch2 Regulates the Function of Bovine Follicular Granulosa Cells via the Wnt2/β-Catenin Signaling Pathway |
title_full | Notch2 Regulates the Function of Bovine Follicular Granulosa Cells via the Wnt2/β-Catenin Signaling Pathway |
title_fullStr | Notch2 Regulates the Function of Bovine Follicular Granulosa Cells via the Wnt2/β-Catenin Signaling Pathway |
title_full_unstemmed | Notch2 Regulates the Function of Bovine Follicular Granulosa Cells via the Wnt2/β-Catenin Signaling Pathway |
title_short | Notch2 Regulates the Function of Bovine Follicular Granulosa Cells via the Wnt2/β-Catenin Signaling Pathway |
title_sort | notch2 regulates the function of bovine follicular granulosa cells via the wnt2 β catenin signaling pathway |
topic | Notch2 Wnt2/β-catenin bovine follicular granulosa cells interaction |
url | https://www.mdpi.com/2076-2615/14/7/1001 |
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