Hic-5 regulates an epithelial program mediated by PPARγ
Open Access
- 1 February 2005
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 19 (3) , 362-375
- https://doi.org/10.1101/gad.1240705
Abstract
PPARγ is a dominant regulator of fat cell differentiation. However, this nuclear receptor also plays an important role in the differentiation of intestinal and other epithelial cell types. The mechanism by which PPARγ can influence the differentiation of such diverse cell lineages is unknown. We show here that PPARγ interacts with Hic-5, a coactivator protein expressed in gut epithelial cells. Hic-5 and PPARγ colocalize to the villus epithelium of the small intestine, and their expression during embryonic gut development correlates with the transition from endoderm to a specialized epithelium; expression of both these factors is reduced in tumors. Forced expression of Hic-5 in colon cancer cells enhances the PPARγ-mediated induction of several gut epithelial differentiation/maturation markers such as L-FABP, kruppel-like factor 4 (KLF4), and keratin 20. siRNA directed against Hic-5 specifically reduces PPARγ-mediated induction of gut epithelial genes in colon cells and in an ex vivo model of embryonic gut differentiation. Finally, forced expression of Hic-5 during 3T3-L1 preadipocyte differentiation inhibits adipogenesis while inducing inappropriate expression of several mRNAs characteristic of gut epithelium in these mesenchymal cells. These results indicate that Hic5 is an important component in determining an epithelial differentiation program induced by PPARγ.Keywords
This publication has 76 references indexed in Scilit:
- PGC-1 promotes insulin resistance in liver through PPAR-α-dependent induction of TRB-3Nature Medicine, 2004
- Peroxisome proliferator-activated receptors (PPARs) and associated transcription factors in colon cancer: reduced expression of PPARγ-coactivator 1 (PGC-1)Cancer Letters, 2004
- Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Krüppel-like factorAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2004
- Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecityOncogene, 2003
- Myocardin Is a Key Regulator of CArG-Dependent Transcription of Multiple Smooth Muscle Marker GenesCirculation Research, 2003
- Transcriptional Profiling of Krüppel-like Factor 4 Reveals a Function in Cell Cycle Regulation and Epithelial DifferentiationJournal of Molecular Biology, 2003
- Molecular cloning of human hic-5, a potential regulator involved in signal transduction and cellular senescenceMolecular Carcinogenesis, 2000
- Terminal Differentiation of Human Breast Cancer through PPARγMolecular Cell, 1998
- Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha.Proceedings of the National Academy of Sciences, 1995
- Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factorCell, 1994