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Interaction of C/EBPβ with SMAD2 and SMAD4 genes induces the formation of lipid droplets in bovine myoblasts

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Abstract

As a key component of Transforming growth factor-β (TGF-β) pathway, Smad2 has many crucial roles in a variety of cellular processes, but it cannot bind DNA without complex formation with Smad4. In the present study, the molecular mechanism in the progress of myogenesis underlying transcriptional regulation of SMAD2 and SMAD4 had been clarified. The result showed the inhibition between SMAD2 and SMAD4, which promotes and inhibits bovine myoblast differentiation, respectively. Further, the characterization of promoter region of SMAD2 and SMAD4 was analyzed, and identified C/EBPβ directly bound to the core region of both SMAD2 and SMAD4 genes promoter and stimulated the transcriptional activity. However, C/EBPβ has lower expression in myoblasts which plays vital function in the transcriptional networks controlling adipogenesis, while the overexpression of C/EBPβ gene in myoblasts significantly increased SMAD2 and SMAD4 gene expression, induced the formation of lipid droplet in bovine myoblasts, and promoted the expression of adipogenesis-specific genes. Collectively, our results showed that C/EBPβ may play an important role in the trans-differentiation and dynamic equilibrium of myoblasts into adipocyte cells via promoting an increase in SMAD2 and SMAD4 gene levels. These results will provide an important basis for further understanding of the TGFβ pathway and C/EBPβ gene during myogenic differentiation.

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Data availability

All the data are available within the manuscript. The authors acknowledge that all relevant data presented in this study are contained within the article/material; further inquiries can be directed to the corresponding authors.

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Funding

This research was supported by the Natural Science Foundation of China (82260285, 32202641 and 31960672), the Natural Science Foundation of Ningxia (2021AAC05007), the Natural Science Basic Research Program of Shaanxi (2021JQ-622), the Key R & D projects in Ningxia Hui Autonomous Region (2023BCF01006), the Yan’an University Doctoral Research Initiation Project (YDBK2018-28), the National Modern Agriculture (Beef and Yak) Technology System (CARS-37), and the Scientific Research Plan Projects of Shaanxi Education Department (20JK0444).

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Author notes

  1. Dawei Wei and Le Zhang contributed equally to this work.

Authors and Affiliations

  1. College of Animal Science and Technology, Ningxia University, Yinchuan, 750021, China

    Dawei Wei & Guijie Zhang

  2. Institute of Physical Education, Yan’an University, Yan’an, 716000, China

    Le Zhang

  3. Guangdong Provincial Key Laboratory of Food Quality and Safety/Nation-Local Joint Engineering Research Center for Machining and Safety of Livestock and Poultry Products, South China Agricultural University, Guangzhou, 510642, China

    Sayed Haidar Abbas Raza

  4. College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China

    Sayed Haidar Abbas Raza

  5. Institute of Animal Science, Ningxia Academy of Agriculture and Forestry Sciences, Yinchuan, 750021, China

    Jiupan Zhang & Xiaojun Liang

  6. College of Animal Science and Technology, South China Agricultural University, Guangzhou, 510642, China

    Zhao Juan

  7. Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia

    Hadba Al-Amrah

  8. Department of Pathology, College of Medicine, Qassim University, P.O. Box 6655, Buraidah, 51452, Kingdom of Saudi Arabia

    Waleed Al Abdulmonem

  9. Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, 51452, Saudi Arabia

    Yousef Mesfer Alharbi

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  1. Dawei Wei
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Contributions

Dawei Wei and Le Zhang: conceptualization, data curation, formal analysis, investigation, methodology, software, validation, writing — original draft, writing—review and editing.

Sayed Haidar Abbas Raza and Zhao Juan: conceptualization, data curation, formal analysis, investigation, methodology, software, validation, writing — review and editing.

Guijie Zhang: conceptualization, data curation, formal analysis, methodology, software, validation. Hadba Al-Amrah: formal analysis, writing — review and editing. Waleed Al Abdulmonem: data curation, formal analysis. Yousef Mesfer Alharbi: data curation, formal writing — review and editing, methodology. Jiupan Zhang: supervision, software, methodology, visualization. Xiaojun Liang: conceptualization, funding acquisition, project administration, resources, supervision, visualization, writing — review and editing. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Guijie Zhang or Xiaojun Liang.

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Wei, D., Zhang, L., Raza, S.H.A. et al. Interaction of C/EBPβ with SMAD2 and SMAD4 genes induces the formation of lipid droplets in bovine myoblasts. Funct Integr Genomics 23, 191 (2023). https://doi.org/10.1007/s10142-023-01115-y

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