DKK3 promotes adipogenic differentiation of stem cells by inhibiting Wnt/β-catenin signaling pathway related gene expression and mitochondrial autophagy function

ABSTRACT: Mesenchymal stem cells can differentiate into adipocyte precursor cells, and the balance of stem cell differentiation determines the quantity of adipocytes. Early-stage adipose tissue expression profiling revealed abnormal expression of DKK3 in the high-fat group. Moreover, DKK3 is enriche...

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Main Authors: Ze Zhang, Haohui Wei, Tao Lin, Changbin Zhao, Yongxiang Song, Yuelin Deng, Yiqing Sun, Yongxia Zhao, Qingbin Luo, Xiquan Zhang, Dexiang Zhang, Hongmei Li
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Poultry Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S0032579124008368
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author Ze Zhang
Haohui Wei
Tao Lin
Changbin Zhao
Yongxiang Song
Yuelin Deng
Yiqing Sun
Yongxia Zhao
Qingbin Luo
Xiquan Zhang
Dexiang Zhang
Hongmei Li
author_facet Ze Zhang
Haohui Wei
Tao Lin
Changbin Zhao
Yongxiang Song
Yuelin Deng
Yiqing Sun
Yongxia Zhao
Qingbin Luo
Xiquan Zhang
Dexiang Zhang
Hongmei Li
author_sort Ze Zhang
collection DOAJ
description ABSTRACT: Mesenchymal stem cells can differentiate into adipocyte precursor cells, and the balance of stem cell differentiation determines the quantity of adipocytes. Early-stage adipose tissue expression profiling revealed abnormal expression of DKK3 in the high-fat group. Moreover, DKK3 is enriched in the Wnt/β-catenin signaling pathway, and studies have shown that DKK3 can serve as a gene involved in early regulation of adipogenesis. Therefore, this study focuses on exploring how DKK3 regulates the molecular mechanism of adipocyte differentiation through the Wnt/β-catenin signaling pathway. In this experiment, the role of DKK3 in the differentiation of bone marrow mesenchymal stem cells into adipocyte precursors was validated using in vitro cultured chicken bone marrow mesenchymal stem cells. The results showed that overexpression of DKK3 led to a significant downregulation of Wnt/β-catenin signaling pathway-related marker gene expression (P < 0.05), a significant upregulation of adipogenic differentiation-related genes (P < 0.05), an increase in lipid droplet content, a significant increase in OD value (P < 0.05), a significant upregulation of mitochondrial oxidative respiratory-related marker gene expression (P < 0.05), and a significant downregulation of mitochondrial autophagy-related marker genes (P < 0.05). Conversely, the results were opposite after interfering with DKK3 gene expression. In this study, 4 SNP sites, including g.8419139, g.8419556, g.8419560, and g.8419598, were detected in the 7th exon of DKK3, among which the g.8419598 (C > T) site was significantly correlated with abdominal fat weight and abdominal fat rate in 100-day-old Ma Huang chickens (P < 0.001).
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spelling doaj-art-8c41b595e8c740f58aeca3f64f4d34ba2024-12-14T06:28:40ZengElsevierPoultry Science0032-57912024-12-0110312104257DKK3 promotes adipogenic differentiation of stem cells by inhibiting Wnt/β-catenin signaling pathway related gene expression and mitochondrial autophagy functionZe Zhang0Haohui Wei1Tao Lin2Changbin Zhao3Yongxiang Song4Yuelin Deng5Yiqing Sun6Yongxia Zhao7Qingbin Luo8Xiquan Zhang9Dexiang Zhang10Hongmei Li11Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, China; Department of Animal nutrition system, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong,ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, Guangdong, China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, Guangdong, China; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, Guangdong, China; Corresponding author:ABSTRACT: Mesenchymal stem cells can differentiate into adipocyte precursor cells, and the balance of stem cell differentiation determines the quantity of adipocytes. Early-stage adipose tissue expression profiling revealed abnormal expression of DKK3 in the high-fat group. Moreover, DKK3 is enriched in the Wnt/β-catenin signaling pathway, and studies have shown that DKK3 can serve as a gene involved in early regulation of adipogenesis. Therefore, this study focuses on exploring how DKK3 regulates the molecular mechanism of adipocyte differentiation through the Wnt/β-catenin signaling pathway. In this experiment, the role of DKK3 in the differentiation of bone marrow mesenchymal stem cells into adipocyte precursors was validated using in vitro cultured chicken bone marrow mesenchymal stem cells. The results showed that overexpression of DKK3 led to a significant downregulation of Wnt/β-catenin signaling pathway-related marker gene expression (P < 0.05), a significant upregulation of adipogenic differentiation-related genes (P < 0.05), an increase in lipid droplet content, a significant increase in OD value (P < 0.05), a significant upregulation of mitochondrial oxidative respiratory-related marker gene expression (P < 0.05), and a significant downregulation of mitochondrial autophagy-related marker genes (P < 0.05). Conversely, the results were opposite after interfering with DKK3 gene expression. In this study, 4 SNP sites, including g.8419139, g.8419556, g.8419560, and g.8419598, were detected in the 7th exon of DKK3, among which the g.8419598 (C > T) site was significantly correlated with abdominal fat weight and abdominal fat rate in 100-day-old Ma Huang chickens (P < 0.001).http://www.sciencedirect.com/science/article/pii/S0032579124008368chickenBMSCsWnt-βcatenin signaling pathwaylipogenic differentiationmitochondriaDKK3
spellingShingle Ze Zhang
Haohui Wei
Tao Lin
Changbin Zhao
Yongxiang Song
Yuelin Deng
Yiqing Sun
Yongxia Zhao
Qingbin Luo
Xiquan Zhang
Dexiang Zhang
Hongmei Li
DKK3 promotes adipogenic differentiation of stem cells by inhibiting Wnt/β-catenin signaling pathway related gene expression and mitochondrial autophagy function
Poultry Science
chicken
BMSCs
Wnt-βcatenin signaling pathway
lipogenic differentiation
mitochondria
DKK3
title DKK3 promotes adipogenic differentiation of stem cells by inhibiting Wnt/β-catenin signaling pathway related gene expression and mitochondrial autophagy function
title_full DKK3 promotes adipogenic differentiation of stem cells by inhibiting Wnt/β-catenin signaling pathway related gene expression and mitochondrial autophagy function
title_fullStr DKK3 promotes adipogenic differentiation of stem cells by inhibiting Wnt/β-catenin signaling pathway related gene expression and mitochondrial autophagy function
title_full_unstemmed DKK3 promotes adipogenic differentiation of stem cells by inhibiting Wnt/β-catenin signaling pathway related gene expression and mitochondrial autophagy function
title_short DKK3 promotes adipogenic differentiation of stem cells by inhibiting Wnt/β-catenin signaling pathway related gene expression and mitochondrial autophagy function
title_sort dkk3 promotes adipogenic differentiation of stem cells by inhibiting wnt β catenin signaling pathway related gene expression and mitochondrial autophagy function
topic chicken
BMSCs
Wnt-βcatenin signaling pathway
lipogenic differentiation
mitochondria
DKK3
url http://www.sciencedirect.com/science/article/pii/S0032579124008368
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