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DDIT3 Governs Milk Production Traits by Targeting IL-6 to Induce Apoptosis in Dairy Cattle

Author

Listed:
  • Xiaogang Cui

    (College of Food and Biological Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei 230009, China
    Key Lab of Medical Molecular Cell Biology of Shanxi Province, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi Provincial Key Laboratory for Major Infectious Disease Response, Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China)

  • Changqing Li

    (College of Food and Biological Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei 230009, China)

  • Zhangqi Wei

    (College of Food and Biological Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei 230009, China)

  • Hangting Meng

    (Key Lab of Medical Molecular Cell Biology of Shanxi Province, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi Provincial Key Laboratory for Major Infectious Disease Response, Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China)

  • Fengfeng Zhang

    (Key Lab of Medical Molecular Cell Biology of Shanxi Province, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi Provincial Key Laboratory for Major Infectious Disease Response, Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China)

  • Yue Liu

    (Key Lab of Medical Molecular Cell Biology of Shanxi Province, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi Provincial Key Laboratory for Major Infectious Disease Response, Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China)

  • Changxin Wu

    (Key Lab of Medical Molecular Cell Biology of Shanxi Province, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi Provincial Key Laboratory for Major Infectious Disease Response, Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China)

  • Shaohua Yang

    (College of Food and Biological Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei 230009, China
    College of Animal Science and Technology, China Agricultural University, Beijing 100193, China)

Abstract

The mechanisms of modulating milk production traits remain largely unknown. Based on our previous RNA-seq, DDIT3 was presumed as a novel, promising candidate gene for regulating milk protein and fat traits in dairy cattle. To further detect the genetic effect of DDIT3 and its potential molecular mechanisms in regulating milk production traits in dairy cattle, here, we performed a genotype-phenotype association study. Two SNPs, g.-1194 C>T and g.-128 C>T, were significantly associated with MY ( p = 0.0063), FY ( p = 0.0001) and PY ( p = 0.0216), respectively. A luciferase assay demonstrated that the allele T of g.-128 C>T increased the promoter activity by binding the HSF2, while allele C did not. To further reveal the molecular regulatory mechanisms, the DDIT3 -knockdown MAC-T cells were established. It was observed that DDIT3 silencing could induce apoptosis and increase the number of PI-positive cells. Meanwhile, DDIT3 silencing led to increased expression of inflammatory markers, such as IL-6 , IL6R , IL1B , IL7R , IL1RL2 , IL1A , STAT1-5 , MYC , IGFBP4, and IGFBP5 , and especially for IL-6 (log 2 FC = 4.22; p = 3.49 × 10 −112 ). Additionally, compared with the control group, increased lipid accumulation was found in the DDIT3 -knockdown MAC-T cells. Thus, our results proved that lower expression of DDIT3 could result in increased lipid accumulation and apoptosis via up-regulating the expression of IL-6. These findings provided clues about the regulatory mechanisms of milk production traits in dairy cattle.

Suggested Citation

  • Xiaogang Cui & Changqing Li & Zhangqi Wei & Hangting Meng & Fengfeng Zhang & Yue Liu & Changxin Wu & Shaohua Yang, 2022. "DDIT3 Governs Milk Production Traits by Targeting IL-6 to Induce Apoptosis in Dairy Cattle," Agriculture, MDPI, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:gam:jagris:v:13:y:2022:i:1:p:117-:d:1021764
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