help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on May 12, 2005
Molecular Endocrinology, doi:10.1210/me.2005-0068
Molecular Endocrinology Vol. 0, No. 2005 200500681-
doi:10.1210/me.2005-0068
Copyright © 2005 by the Endocrine Society.
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
19/9/2335    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow NURSA Molecule Pages Link
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Michalik, L.
Right arrow Articles by Wahli, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Michalik, L.
Right arrow Articles by Wahli, W.

Submitted on January 29, 2005
Accepted on May 2, 2005

Selective expression of a dominant negative form of PPAR in keratinocytes leads to impaired epidermal healing

L. Michalik*, J. N. Feige, L. Gelman, T. Pedrazzini, H. Keller, B. Desvergne, and W. Wahli*

Center for Integrative Genomics, NCCR Frontiers in Genetics, University of Lausanne, Switzerland; Department of Medicine, University of Lausanne, Switzerland; Present address: Novartis Institutes for Biomedical Research, Basel, Switzerland

* To whom correspondence should be addressed. E-mail: liliane.michalik{at}unil.ch or walter.wahli{at}unil.ch.

Many nuclear hormone receptors are involved in the regulation of skin homeostasis. However, their role in the epithelial compartment of the skin in stress situations, such as skin healing, has not been addressed yet. The healing of a skin wound after an injury involves three major cell types: immune cells, which are recruited to the wound bed, dermal fibroblasts, and epidermal and hair follicle keratinocytes. Our previous studies have revealed important but non redundant roles of PPAR{alpha} and {beta}/d in the reparation of the skin after a mechanical injury in the adult mouse. However, the mesenchymal or epithelial cellular compartment in which PPAR{alpha} and {beta} play a role could not be determined in the null mice used, which have a germ line PPAR gene invalidation. In the present work, the role of PPAR{alpha} was studied in keratinocytes, using transgenic mice which express a PPAR{alpha} mutant with dominant negative (dn) activity specifically in keratinocytes. This dn PPAR{alpha} lacks the last 13 C-terminus amino acids, binds to PPAR{alpha} agonist, but is unable to release the corepressor NCoR and to recruit the coactivator p300. When selectively expressed in keratinocytes of transgenic mice dn PPAR{alpha}{Delta}13 causes a delay in the healing of skin wounds, accompanied by an exacerbated inflammation. This phenotype, which is similar to that observed in PPAR{alpha} null mice, strongly suggests that during skin healing, PPAR{alpha} is required in keratinocytes rather than in other cell types.
Key words: PPAR • AF2 function • dominant negative mutant • transgenic mouse • skin healing

NURSA Molecule Pages Link:

Nuclear Receptors:   RARα  |  RARβ  |  RARγ  |  PPARα  |  PPARδ  |  PPARγ  |  RXRβ
Coregulators:   p300  |  NCOR
Ligands:   all-trans-Retinoic acid  |  Pirinixic acid  |  Rosiglitazone



This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
M. H. Liu, J. Li, P. Shen, B. Husna, E. S. Tai, and E. L. Yong
A Natural Polymorphism in Peroxisome Proliferator-Activated Receptor-{alpha} Hinge Region Attenuates Transcription due to Defective Release of Nuclear Receptor Corepressor from Chromatin
Mol. Endocrinol., May 1, 2008; 22(5): 1078 - 1092.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Tudor, J. N. Feige, H. Pingali, V. B. Lohray, W. Wahli, B. Desvergne, Y. Engelborghs, and L. Gelman
Association with Coregulators Is the Major Determinant Governing Peroxisome Proliferator-activated Receptor Mobility in Living Cells
J. Biol. Chem., February 16, 2007; 282(7): 4417 - 4426.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
L. Michalik, J. Auwerx, J. P. Berger, V. K. Chatterjee, C. K. Glass, F. J. Gonzalez, P. A. Grimaldi, T. Kadowaki, M. A. Lazar, S. O'Rahilly, et al.
International Union of Pharmacology. LXI. Peroxisome Proliferator-Activated Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 726 - 741.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
M. A. Peraza, A. D. Burdick, H. E. Marin, F. J. Gonzalez, and J. M. Peters
The Toxicology of Ligands for Peroxisome Proliferator-Activated Receptors (PPAR)
Toxicol. Sci., April 1, 2006; 90(2): 269 - 295.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2005 by The Endocrine Society