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PMID: 12101242 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Nrf2 transcription factor, a novel target of keratinocyte growth factor action which regulates gene expression and inflammation in the healing skin wound.

Molecular and cellular biology ·Vol. 22 ·No. 15 ·2002-08-00 ·Pages 5492-505

Braun S, Hanselmann C, Gassmann MG, auf dem Keller U, Born-Berclaz C, Chan K, Kan YW, Werner S

Abstract

Keratinocyte growth factor (KGF) is a potent mitogen for epithelial cells, and it promotes survival of these cells under stress conditions. In a search for KGF-regulated genes in keratinocytes, we identified the gene encoding the transcription factor NF-E2-related factor 2 (Nrf2). Nrf2 is a key player in the cellular stress response. This might be of particular importance during wound healing, where large amounts of reactive oxygen species are produced as a defense against invading bacteria. Therefore, we studied the wound repair process in Nrf2 knockout mice. Interestingly, the expression of various key players involved in wound healing was significantly reduced in early wounds of the Nrf2 knockout animals, and the late phase of repair was characterized by prolonged inflammation. However, these differences in gene expression were not reflected by obvious histological abnormalities. The normal healing rate appears to be at least partially due to an up-regulation of the related transcription factor Nrf3, which was also identified as a target of KGF and which was coexpressed with Nrf2 in the healing skin wound. Taken together, our results reveal novel roles of the KGF-regulated transcription factors Nrf2 and possibly Nrf3 in the control of gene expression and inflammation during cutaneous wound repair.

MeSH Terms
Animals Basic-Leucine Zipper Transcription Factors Blotting, Western Cell Line Cytokines/metabolism DNA-Binding Proteins/deficiency,genetics,metabolism Disease Models, Animal Extracellular Matrix/metabolism Fibroblast Growth Factor 7 Fibroblast Growth Factors/pharmacology Gene Expression Regulation/drug effects,physiology Glutathione Transferase/genetics,metabolism Heme Oxygenase (Decyclizing)/genetics,metabolism Heme Oxygenase-1 Humans Inflammation/metabolism,pathology Keratinocytes/drug effects,metabolism,pathology Membrane Proteins Mice Mice, Inbred BALB C Mice, Knockout NF-E2-Related Factor 2 Oxidative Stress RNA, Messenger/metabolism Skin/drug effects,injuries,pathology Trans-Activators/deficiency,genetics,metabolism Transcription Factors/metabolism Wound Healing/drug effects,physiology
Chemicals
Basic-Leucine Zipper Transcription Factors Cytokines DNA-Binding Proteins FGF7 protein, human Fgf7 protein, mouse Membrane Proteins NF-E2-Related Factor 2 NFE2L2 protein, human NFE2L3 protein, human Nfe2l2 protein, mouse RNA, Messenger Trans-Activators Transcription Factors Fibroblast Growth Factor 7 Fibroblast Growth Factors HMOX1 protein, human Heme Oxygenase (Decyclizing) Heme Oxygenase-1 Hmox1 protein, mouse Glutathione Transferase
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Braun Susanne
Institute of Cell Biology, Department of Biology, ETH Zürich, Hönggerberg, CH-8093 Zürich, Switzerland.
Hanselmann Christine
Gassmann Marcus G
auf dem Keller Ulrich
Born-Berclaz Christiane
Chan Kaimin
Kan Yuet Wai
Werner Sabine
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.22.15.5492-5505.2002
Published
2002-08-00
Pages
5492-505
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC133949
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.22.15.5492-5505.2002 PMC Full Text View journal details
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