The Mechanisms of BDNF Promoting the Proliferation of Porcine Follicular Granulosa Cells: Role of miR-127 and Involvement of the MAPK-ERK1/2 Pathway

As a member of the neurotrophic family, brain-derived neurotrophic factor (BDNF) provides a key link in the physiological process of mammalian ovarian follicle development, in addition to its functions in the nervous system. The emphasis of this study lay in the impact of BDNF on the proliferation o...

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Main Authors: Xue Zheng, Lu Chen, Tong Chen, Maosheng Cao, Boqi Zhang, Chenfeng Yuan, Zijiao Zhao, Chunjin Li, Xu Zhou
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Animals
Subjects:
Online Access:https://www.mdpi.com/2076-2615/13/6/1115
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author Xue Zheng
Lu Chen
Tong Chen
Maosheng Cao
Boqi Zhang
Chenfeng Yuan
Zijiao Zhao
Chunjin Li
Xu Zhou
author_facet Xue Zheng
Lu Chen
Tong Chen
Maosheng Cao
Boqi Zhang
Chenfeng Yuan
Zijiao Zhao
Chunjin Li
Xu Zhou
author_sort Xue Zheng
collection DOAJ
description As a member of the neurotrophic family, brain-derived neurotrophic factor (BDNF) provides a key link in the physiological process of mammalian ovarian follicle development, in addition to its functions in the nervous system. The emphasis of this study lay in the impact of BDNF on the proliferation of porcine follicular granulosa cells (GCs) in vitro. BDNF and tyrosine kinase B (TrkB, receptor of BDNF) were detected in porcine follicular GCs. Additionally, cell viability significantly increased during the culture of porcine GCs with BDNF (100 ng/mL) in vitro. However, BDNF knockdown in GCs decreased cell viability and S-phase cells proportion—and BDNF simultaneously regulated the expression of genes linked with cell proliferation (CCND1, p21 and Bcl2) and apoptosis (Bax). Then, the results of the receptor blocking experiment showed that BDNF promoted GC proliferation via TrkB. The high-throughput sequencing showed that BDNF also regulated the expression profiles of miRNAs in GCs. The differential expression profiles were obtained by miRNA sequencing after BDNF (100 ng/mL) treatment with GCs. The sequencing results showed that, after BDNF treatment, 72 significant differentially-expressed miRNAs were detected—5 of which were related to cell process and proliferation signaling pathways confirmed by RT-PCR. Furthermore, studies showed that BDNF promoted GCs’ proliferation by increasing the expression of CCND1, downregulating miR-127 and activating the ERK1/2 signal pathway. Moreover, BDNF indirectly activated the ERK1/2 signal pathway by downregulating miR-127. In conclusion, BDNF promoted porcine GC proliferation by increasing CCND1 expression, downregulating miR-127 and stimulating the MAPK-ERK1/2 signaling cascade.
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spelling doaj.art-da57c633b0444cd9bd8b4fde6106042d2023-11-17T09:12:36ZengMDPI AGAnimals2076-26152023-03-01136111510.3390/ani13061115The Mechanisms of BDNF Promoting the Proliferation of Porcine Follicular Granulosa Cells: Role of miR-127 and Involvement of the MAPK-ERK1/2 PathwayXue Zheng0Lu Chen1Tong Chen2Maosheng Cao3Boqi Zhang4Chenfeng Yuan5Zijiao Zhao6Chunjin Li7Xu Zhou8Laboratory for Regulation of Reproduction, College of Animal Sciences, Jilin University, Changchun 130062, ChinaLaboratory for Regulation of Reproduction, College of Animal Sciences, Jilin University, Changchun 130062, ChinaLaboratory for Regulation of Reproduction, College of Animal Sciences, Jilin University, Changchun 130062, ChinaLaboratory for Regulation of Reproduction, College of Animal Sciences, Jilin University, Changchun 130062, ChinaLaboratory for Regulation of Reproduction, College of Animal Sciences, Jilin University, Changchun 130062, ChinaLaboratory for Regulation of Reproduction, College of Animal Sciences, Jilin University, Changchun 130062, ChinaLaboratory for Regulation of Reproduction, College of Animal Sciences, Jilin University, Changchun 130062, ChinaLaboratory for Regulation of Reproduction, College of Animal Sciences, Jilin University, Changchun 130062, ChinaLaboratory for Regulation of Reproduction, College of Animal Sciences, Jilin University, Changchun 130062, ChinaAs a member of the neurotrophic family, brain-derived neurotrophic factor (BDNF) provides a key link in the physiological process of mammalian ovarian follicle development, in addition to its functions in the nervous system. The emphasis of this study lay in the impact of BDNF on the proliferation of porcine follicular granulosa cells (GCs) in vitro. BDNF and tyrosine kinase B (TrkB, receptor of BDNF) were detected in porcine follicular GCs. Additionally, cell viability significantly increased during the culture of porcine GCs with BDNF (100 ng/mL) in vitro. However, BDNF knockdown in GCs decreased cell viability and S-phase cells proportion—and BDNF simultaneously regulated the expression of genes linked with cell proliferation (CCND1, p21 and Bcl2) and apoptosis (Bax). Then, the results of the receptor blocking experiment showed that BDNF promoted GC proliferation via TrkB. The high-throughput sequencing showed that BDNF also regulated the expression profiles of miRNAs in GCs. The differential expression profiles were obtained by miRNA sequencing after BDNF (100 ng/mL) treatment with GCs. The sequencing results showed that, after BDNF treatment, 72 significant differentially-expressed miRNAs were detected—5 of which were related to cell process and proliferation signaling pathways confirmed by RT-PCR. Furthermore, studies showed that BDNF promoted GCs’ proliferation by increasing the expression of CCND1, downregulating miR-127 and activating the ERK1/2 signal pathway. Moreover, BDNF indirectly activated the ERK1/2 signal pathway by downregulating miR-127. In conclusion, BDNF promoted porcine GC proliferation by increasing CCND1 expression, downregulating miR-127 and stimulating the MAPK-ERK1/2 signaling cascade.https://www.mdpi.com/2076-2615/13/6/1115BDNFporcineproliferationmicroRNACCND1ERK
spellingShingle Xue Zheng
Lu Chen
Tong Chen
Maosheng Cao
Boqi Zhang
Chenfeng Yuan
Zijiao Zhao
Chunjin Li
Xu Zhou
The Mechanisms of BDNF Promoting the Proliferation of Porcine Follicular Granulosa Cells: Role of miR-127 and Involvement of the MAPK-ERK1/2 Pathway
Animals
BDNF
porcine
proliferation
microRNA
CCND1
ERK
title The Mechanisms of BDNF Promoting the Proliferation of Porcine Follicular Granulosa Cells: Role of miR-127 and Involvement of the MAPK-ERK1/2 Pathway
title_full The Mechanisms of BDNF Promoting the Proliferation of Porcine Follicular Granulosa Cells: Role of miR-127 and Involvement of the MAPK-ERK1/2 Pathway
title_fullStr The Mechanisms of BDNF Promoting the Proliferation of Porcine Follicular Granulosa Cells: Role of miR-127 and Involvement of the MAPK-ERK1/2 Pathway
title_full_unstemmed The Mechanisms of BDNF Promoting the Proliferation of Porcine Follicular Granulosa Cells: Role of miR-127 and Involvement of the MAPK-ERK1/2 Pathway
title_short The Mechanisms of BDNF Promoting the Proliferation of Porcine Follicular Granulosa Cells: Role of miR-127 and Involvement of the MAPK-ERK1/2 Pathway
title_sort mechanisms of bdnf promoting the proliferation of porcine follicular granulosa cells role of mir 127 and involvement of the mapk erk1 2 pathway
topic BDNF
porcine
proliferation
microRNA
CCND1
ERK
url https://www.mdpi.com/2076-2615/13/6/1115
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