Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-9-29
pubmed:abstractText
Our recent studies have demonstrated that PPARalpha activators stimulate differentiation and inhibit proliferation in cultured human keratinocytes and accelerate epidermal development and permeability barrier formation in fetal rat skin explants. As the role of PPARalpha activation in adult epidermis is not known, the aim of this study was to determine if topically applied PPARalpha ligands regulate keratinocyte differentiation in murine epidermis. Topical treatment with PPARalpha activators resulted in decreased epidermal thickness. Expression of structural proteins of the upper spinous/granular layers (involucrin, profilaggrin-filaggrin, loricrin) increased following topical treatment with PPARalpha activators. Furthermore, topically applied PPARalpha activators also increased apoptosis, decreased cell proliferation, and accelerated recovery of barrier function following acute barrier abrogation. Experiments with PPARalpha-/- knockout mice showed that these effects are specifically mediated via PPARalpha. Compared with the epidermis of PPARalpha+/+ mice, involucrin, profilaggrin-filaggrin, and loricrin expression were slightly decreased in PPARalpha-/- mice. Moreover, topical clofibrate treatment did not increase epidermal differentiation in PPARalpha-/- mice. Furthermore, in cultured human keratinocytes we have demonstrated that PPARalpha activators induce an increase in involucrin mRNA levels. We have also shown that this increase in gene expression requires an intact AP-1 response element at -2117 to -2111 bp. Thus, stimulation of PPARalpha stimulates keratinocyte/epidermal differentiation and inhibits proliferation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-202X
pubmed:author
pubmed:issnType
Print
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
353-60
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10951268-Administration, Cutaneous, pubmed-meshheading:10951268-Animals, pubmed-meshheading:10951268-Apoptosis, pubmed-meshheading:10951268-Cell Differentiation, pubmed-meshheading:10951268-Cell Division, pubmed-meshheading:10951268-Clofibrate, pubmed-meshheading:10951268-Keratinocytes, pubmed-meshheading:10951268-Male, pubmed-meshheading:10951268-Mice, pubmed-meshheading:10951268-Mice, Hairless, pubmed-meshheading:10951268-Permeability, pubmed-meshheading:10951268-Promoter Regions, Genetic, pubmed-meshheading:10951268-Protein Precursors, pubmed-meshheading:10951268-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:10951268-Skin, pubmed-meshheading:10951268-Transcription, Genetic, pubmed-meshheading:10951268-Transcription Factor AP-1, pubmed-meshheading:10951268-Transcription Factors
pubmed:year
2000
pubmed:articleTitle
Stimulation of PPARalpha promotes epidermal keratinocyte differentiation in vivo.
pubmed:affiliation
Departments of Dermatology, Medicine, and Pediatrics, University of California, San Francisco School of Medicine, San Francisco, California, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't