PPARβ/δ selectively induces differentiation and inhibits cell proliferation

D. J. Kim; M. T. Bility; A. N. Billin; T. M. Willson; F. J. Gonzalez; J. M. Peters

doi:10.1038/sj.cdd.4401713

PPARβ/δ selectively induces differentiation and inhibits cell proliferation

D. J. Kim, M. T. Bility, A. N. Billin, T. M. Willson, F. J. Gonzalez, J. M. Peters

Pharmacology

Research output: Contribution to journal › Article › peer-review

118 Scopus citations

Abstract

Peroxisome proliferator-activated receptor (PPAR) β-null mice exhibit exacerbated epithelial cell proliferation and enhanced sensitivity to skin carcinogenesis, suggesting that ligand activation of PPARβ will inhibit keratinocyte proliferation. By using of a highly specific ligand (GW0742) and the PPARβ-null mouse model, activation of PPARβ was found to selectively induce keratinocyte terminal differentiation and inhibit keratinocyte proliferation. Additionally, GW0742 was found to be anti-inflammatory due to inhibition of myeloperoxidase activity, independent of PPARβ. These data suggest that ligand activation of PPARβ could be a novel approach to selectively induce differentiation and inhibit cell proliferation, thus representing a new molecular target for the treatment of skin disorders resulting from altered cell proliferation such as psoriasis and cancer.

Original language	English (US)
Pages (from-to)	53-60
Number of pages	8
Journal	Cell Death and Differentiation
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/sj.cdd.4401713
State	Published - Jan 2006

Keywords

Anti-inflammatory
Cell proliferation
Differentiation
Ligand activation
Null mouse
Peroxisome proliferator-activated receptor-β

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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title = "PPARβ/δ selectively induces differentiation and inhibits cell proliferation",

abstract = "Peroxisome proliferator-activated receptor (PPAR) β-null mice exhibit exacerbated epithelial cell proliferation and enhanced sensitivity to skin carcinogenesis, suggesting that ligand activation of PPARβ will inhibit keratinocyte proliferation. By using of a highly specific ligand (GW0742) and the PPARβ-null mouse model, activation of PPARβ was found to selectively induce keratinocyte terminal differentiation and inhibit keratinocyte proliferation. Additionally, GW0742 was found to be anti-inflammatory due to inhibition of myeloperoxidase activity, independent of PPARβ. These data suggest that ligand activation of PPARβ could be a novel approach to selectively induce differentiation and inhibit cell proliferation, thus representing a new molecular target for the treatment of skin disorders resulting from altered cell proliferation such as psoriasis and cancer.",

keywords = "Anti-inflammatory, Cell proliferation, Differentiation, Ligand activation, Null mouse, Peroxisome proliferator-activated receptor-β",

author = "Kim, {D. J.} and Bility, {M. T.} and Billin, {A. N.} and Willson, {T. M.} and Gonzalez, {F. J.} and Peters, {J. M.}",

note = "Funding Information: We gratefully acknowledge Squire Booker, David Iwig, Adam Glick and Ulrike Lichti for providing technical advice, and Stuart Yuspa and Robert Rice for providing cDNA probes. This work supported by The National Institutes of Health, CA89607, CA97999 (JMP).",

year = "2006",

month = jan,

doi = "10.1038/sj.cdd.4401713",

language = "English (US)",

volume = "13",

pages = "53--60",

journal = "Cell Death and Differentiation",

issn = "1350-9047",

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T1 - PPARβ/δ selectively induces differentiation and inhibits cell proliferation

AU - Kim, D. J.

AU - Bility, M. T.

AU - Billin, A. N.

AU - Willson, T. M.

AU - Gonzalez, F. J.

AU - Peters, J. M.

N1 - Funding Information: We gratefully acknowledge Squire Booker, David Iwig, Adam Glick and Ulrike Lichti for providing technical advice, and Stuart Yuspa and Robert Rice for providing cDNA probes. This work supported by The National Institutes of Health, CA89607, CA97999 (JMP).

PY - 2006/1

Y1 - 2006/1

N2 - Peroxisome proliferator-activated receptor (PPAR) β-null mice exhibit exacerbated epithelial cell proliferation and enhanced sensitivity to skin carcinogenesis, suggesting that ligand activation of PPARβ will inhibit keratinocyte proliferation. By using of a highly specific ligand (GW0742) and the PPARβ-null mouse model, activation of PPARβ was found to selectively induce keratinocyte terminal differentiation and inhibit keratinocyte proliferation. Additionally, GW0742 was found to be anti-inflammatory due to inhibition of myeloperoxidase activity, independent of PPARβ. These data suggest that ligand activation of PPARβ could be a novel approach to selectively induce differentiation and inhibit cell proliferation, thus representing a new molecular target for the treatment of skin disorders resulting from altered cell proliferation such as psoriasis and cancer.

AB - Peroxisome proliferator-activated receptor (PPAR) β-null mice exhibit exacerbated epithelial cell proliferation and enhanced sensitivity to skin carcinogenesis, suggesting that ligand activation of PPARβ will inhibit keratinocyte proliferation. By using of a highly specific ligand (GW0742) and the PPARβ-null mouse model, activation of PPARβ was found to selectively induce keratinocyte terminal differentiation and inhibit keratinocyte proliferation. Additionally, GW0742 was found to be anti-inflammatory due to inhibition of myeloperoxidase activity, independent of PPARβ. These data suggest that ligand activation of PPARβ could be a novel approach to selectively induce differentiation and inhibit cell proliferation, thus representing a new molecular target for the treatment of skin disorders resulting from altered cell proliferation such as psoriasis and cancer.

KW - Anti-inflammatory

KW - Cell proliferation

KW - Differentiation

KW - Ligand activation

KW - Null mouse

KW - Peroxisome proliferator-activated receptor-β

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