Linked Life Data

15644206

Source:http://linkedlifedata.com/resource/pubmed/id/15644206

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-1-12
pubmed:abstractText
Wound healing in its complexity depends on the concerted activity of many signaling pathways. Here, we analyzed how the simultaneous presence of glucocorticoids (GC), retinoic acid (RA) and epidermal growth factor (EGF) affect wound healing at the molecular, cellular and tissue levels. We found that GC inhibit wound healing by inhibiting keratinocyte migration, whereas RA does not. Furthermore, GC block EGF-mediated migration, whereas RA does not. On the molecular level, these compounds target expression of one of the earliest markers of wound healing, cytoskeletal components, keratins K6 and K16. Both GC and RA repress their transcription, whereas EGF induces it. Interestingly, the GC inhibition is mediated by a repressosome complex consisting of four monomers of the GC receptor, beta-catenin and coactivator-associated-arginine-methyltransferase-1. GC are dominant, EGF cannot rescue GC-mediated inhibition. Pre-treatment of keratinocytes with GC shifts the balance towards the repressosome, allowing for dominant inhibition of K6 even in the presence of EGF or c-fos/c-jun. Although RA receptor gamma and glucocorticoid receptor bind to the same response element repressing transcription of keratins K6/K16, RA receptor interacts with the components of the EGF-enhanceosome (co-activators: glucocorticoid-receptor-interactive protein-1(GRIP-1)/steroid-receptors coactivator-1 (SRC-1)) without breaking it. Consequently, RA has a co-dominant effect with EGF: when present simultaneously, their effects balance each other. When keratinocytes are pre-treated with mitogen-activated protein kinase (MAPK) inhibitor, thus blocking EGF, the balance is shifted towards the RA repression. Similar to clinical findings, pre-treatment of keratinocytes with RA blocks GC-mediated inhibition. In summary, our results identify complex molecular mechanisms through which RA alleviates GC-mediated inhibition of wound healing.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
345
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1083-97
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15644206-Base Sequence, pubmed-meshheading:15644206-Cell Movement, pubmed-meshheading:15644206-Cells, Cultured, pubmed-meshheading:15644206-Down-Regulation, pubmed-meshheading:15644206-Epidermal Growth Factor, pubmed-meshheading:15644206-Glucocorticoids, pubmed-meshheading:15644206-Humans, pubmed-meshheading:15644206-Keratinocytes, pubmed-meshheading:15644206-Keratins, pubmed-meshheading:15644206-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:15644206-Molecular Sequence Data, pubmed-meshheading:15644206-Protein Kinase Inhibitors, pubmed-meshheading:15644206-Skin, pubmed-meshheading:15644206-Transcription, Genetic, pubmed-meshheading:15644206-Transcription Factor AP-1, pubmed-meshheading:15644206-Tretinoin, pubmed-meshheading:15644206-Up-Regulation, pubmed-meshheading:15644206-Wound Healing
pubmed:year
2005
pubmed:articleTitle
From an enhanceosome to a repressosome: molecular antagonism between glucocorticoids and EGF leads to inhibition of wound healing.
pubmed:affiliation
New York University School of Medicine, The Ronald O. Perelman Department of Dermatology, 550 First Avenue, New York, NY 10016, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't