Functional & Integrative Genomics

, Volume 7, Issue 3, pp 193–205

Pathway analysis identifies perturbation of genetic networks induced by butyrate in a bovine kidney epithelial cell line

  • Cong-jun Li
  • Robert W Li
  • Yong-hong Wang
  • Ted H. Elsasser
Original Paper


Ruminant species have evolved to metabolize the short-chain volatile fatty acids (VFA), acetate, propionate, and butyrate, to fulfill up to 70% of their nutrient energy requirements. The inherent VFA dependence of ruminant cells was exploited to add a level of increased sensitivity to the study of the role of butyrate gene-response elements in regulatory biochemical pathways. Global gene expression profiles of the bovine kidney epithelial cells regulated by sodium butyrate were investigated with high-density oligonucleotide microarrays. The detailed mechanisms by which butyrate induces cell growth arrest and apoptosis were analyzed using the Ingenuity Pathways Knowledge Base. The functional category and pathway analyses of the microarray data revealed that four canonical pathways (Cell cycles: G2/M DNA damage checkpoint, and pyrimidine metabolism; G1/S checkpoint regulation and purine metabolism) were significantly perturbed. The biologically relevant networks and pathways of these genes were also identified. IGF2, TGFB1, TP53, E2F4, and CDC2 were established as being centered in these genomic networks. The present findings provide a basis for understanding the full range of the biological roles and the molecular mechanisms that butyrate may play in animal cell growth, proliferation, and energy metabolisms.


Apoptosis Butyrate Cell cycle Genetic network 

Supplementary material

10142_2006_43_MOESM1_ESM.doc (268 kb)
Electronic Supplementary Material Table S1List of Focus genes (DOC 268 KB)
10142_2006_43_MOESM2_ESM.doc (50 kb)
Electronic Supplemental Material Table S2Global Functional Analysis. major functions and genes involved (DOC 50.0 KB)
10142_2006_43_MOESM3_ESM.doc (31 kb)
Electronic Supplementary Material Table S3List of up-regulated genetic networks (DOC 31.0 KB)
10142_2006_43_MOESM4_ESM.doc (34 kb)
Electronic Supplemental Material Table S4List of down-regulated genetic networks (DOC 34.5 KB)
10142_2006_43_MOESM5_ESM.doc (43 kb)
Electronic Supplemental Materials Table S5Integrated Genomic Networks (DOC 43.0 KB)

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Cong-jun Li
    • 1
  • Robert W Li
    • 2
  • Yong-hong Wang
    • 3
  • Ted H. Elsasser
    • 1
  1. 1.Growth Biology LaboratoryAnimal and Natural Resources Institute, ARS, USDABeltsvilleUSA
  2. 2.Bovine Functional Genomic LaboratoryAnimal and Natural Resources Institute, ARS, USDABeltsvilleUSA
  3. 3.SAIC-FrederickNCI-FrederickFrederickUSA

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