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Reverse crosstalk of TGFβ and PPARβ/δ signaling identified by transcriptional profiling

Josefine Stockert1, Till Adhikary, Kerstin Kaddatz

  • 1Institute of Molecular Biology and Tumor Research (IMT), Philipps-University, Marburg, Germany.

Nucleic Acids Research
|September 18, 2010
PubMed

Insights

Transforming growth factor-β (TGFβ) and peroxisome proliferator-activated receptor β/δ (PPARβ/δ) signaling pathways exhibit significant crosstalk. PPARβ/δ influences TGFβ-regulated genes in both directions, impacting inflammation and tumor stroma.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) and transforming growth factor-β (TGFβ) are implicated in inflammation and tumor stroma.
  • The potential interconnection between PPARβ/δ and TGFβ signaling remains largely unexplored.

Purpose of the Study:

  • To investigate the crosstalk between PPARβ/δ and TGFβ signaling pathways.
  • To identify gene expression patterns resulting from the interplay of these two pathways.

Main Methods:

  • Microarray analysis of human diploid fibroblasts undergoing myofibroblastic differentiation.
  • Assessment of gene expression changes in response to TGFβ and PPARβ/δ activation.

Main Results:

  • Identified substantial, predominantly reverse crosstalk between PPARβ/δ and TGFβ pathways.
  • Discovered distinct gene classes: PPAR target genes repressed by TGFβ but activated by PPARβ/δ, and TGFβ-induced genes downregulated by PPARβ/δ agonists.
  • Observed cooperative regulation of cell proliferation genes by both pathways.

Conclusions:

  • PPARβ/δ signaling modulates TGFβ-regulated genes in both directions, influencing inflammation and tumor stroma.
  • Integration of TGFβ and PPARβ/δ signals occurs via chromatin-associated complexes, involving corepressor SMRT.
  • Findings highlight the complex regulatory network between PPARβ/δ and TGFβ in cellular processes.

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