Name
Title | ||
|---|---|---|
Reverse crosstalk of TGFβ and PPARβ/δ signaling identified by transcriptional profiling. |
Abstract | ||
|---|---|---|
Previous work has provided strong evidence for a role of peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) and transforming growth factor-beta (TGF beta) in inflammation and tumor stroma function, raising the possibility that both signaling pathways are interconnected. We have addressed this hypothesis by microarray analyses of human diploid fibroblasts induced to myofibroblastic differentiation, which revealed a substantial, mostly reverse crosstalk of both pathways and identified distinct classes of genes. A major class encompasses classical PPAR target genes, including ANGPTL4, CPT1A, ADRP and PDK4. These genes are repressed by TGF beta, which is counteracted by PPAR beta/delta activation. This is mediated, at least in part, by the TGF beta-induced recruitment of the corepressor SMRT to PPAR response elements, and its release by PPAR beta/delta ligands, indicating that TGF beta and PPAR beta/delta signals are integrated by chromatin-associated complexes. A second class represents TGF beta-induced genes that are downregulated by PPAR beta/delta agonists, exemplified by CD274 and IL6, which is consistent with the anti-inflammatory properties of PPAR beta/delta ligands. Finally, cooperative regulation by both ligands was observed for a minor group of genes, including several regulators of cell proliferation. These observations indicate that PPAR beta/delta is able to influence the expression of distinct sets of both TGF beta-repressed and TGF beta-activated genes in both directions. |
Year | DOI | Venue |
|---|---|---|
2011 | 10.1093/nar/gkq773 | NUCLEIC ACIDS RESEARCH |
Keywords | Field | DocType |
gene expression regulation,cell line,cell differentiation,gene expression profiling,transforming growth factor beta,signal transduction,ppar delta,response elements | Corepressor,Transforming growth factor beta,Transforming growth factor,Peroxisome proliferator-activated receptor,Biology,Peroxisome proliferator-activated receptor delta,Cellular differentiation,Regulation of gene expression,Signal transduction,Genetics,Molecular biology | Journal |
Volume | Issue | ISSN |
39 | 1 | 0305-1048 |
Citations | PageRank | References |
7 | 0.47 | 0 |
Authors | ||
7 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Josefine Stockert | 1 | 7 | 0.47 |
| Till Adhikary | 2 | 7 | 0.47 |
| Kerstin Kaddatz | 3 | 7 | 0.47 |
| Florian Finkernagel | 4 | 7 | 0.47 |
| Wolfgang Meissner | 5 | 7 | 0.47 |
| Sabine Müller-Brüsselbach | 6 | 7 | 0.47 |
| R Müller | 7 | 78 | 7.04 |