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PMID: 15687259 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Hic-5 regulates an epithelial program mediated by PPARgamma.

Genes & development ·Vol. 19 ·No. 3 ·2005-02-01 ·Pages 362-75

Drori S, Girnun GD, Tou L, Szwaya JD, Mueller E, Xia K, Kia X, Shivdasani RA, Spiegelman BM

Abstract

PPARgamma 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 PPARgamma can influence the differentiation of such diverse cell lineages is unknown. We show here that PPARgamma interacts with Hic-5, a coactivator protein expressed in gut epithelial cells. Hic-5 and PPARgamma 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 PPARgamma-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 PPARgamma-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 PPARgamma.

MeSH Terms
Adipocytes/cytology,metabolism Animals Cell Differentiation/physiology Colonic Neoplasms/metabolism Cytoskeletal Proteins/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Epithelium/metabolism Gastrointestinal Tract/embryology,metabolism Gene Expression Regulation, Developmental/physiology Kruppel-Like Factor 4 LIM Domain Proteins Mice PPAR gamma/genetics,metabolism RNA, Small Interfering/metabolism
Chemicals
Cytoskeletal Proteins DNA-Binding Proteins Klf4 protein, mouse Kruppel-Like Factor 4 LIM Domain Proteins PPAR gamma RNA, Small Interfering Tgfb1i1 protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Drori Stavit
Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Girnun Geoffrey D
Tou Liqiang
Szwaya Jeffrey D
Mueller Elisabetta
Xia Kai
Kia Xia
Shivdasani Ramesh A
Spiegelman Bruce M
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1240705
Published
2005-02-01
Pages
362-75
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC546514
Subset
IM
Grants
NIDDK NIH HHS · DK064685 · United States
NIDDK NIH HHS · K01 DK064685 · United States
NIDDK NIH HHS · R01DK57670 · United States
NIDDK NIH HHS · R01DK61139 · United States
NIDDK NIH HHS · R01 DK057670 · United States
NIDDK NIH HHS · R01 DK061139 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1101/gad.1240705 PMC Full Text View journal details
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