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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Main Authors: Wenqing Dang, Yongping Ren, Qingqing Chen, Min He, Ermias Kebreab, Dong Wang, Lihua Lyu
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:Animals
Subjects:
Online Access:https://www.mdpi.com/2076-2615/14/7/1001
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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.
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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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