| Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice. | |
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MedLine Citation:
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PMID: 19307725 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The transcription factor serum response factor (SRF) plays a crucial role in the development of several organs. However, its role in the skin has not been explored. Here, we show that keratinocytes in normal human and mouse skin expressed high levels of SRF but that SRF expression was strongly downregulated in the hyperproliferative epidermis of wounded and psoriatic skin. Keratinocyte-specific deletion within the mouse SRF locus during embryonic development caused edema and skin blistering, and all animals died in utero. Postnatal loss of mouse SRF in keratinocytes resulted in the development of psoriasis-like skin lesions. These lesions were characterized by inflammation, hyperproliferation, and abnormal differentiation of keratinocytes as well as by disruption of the actin cytoskeleton. Ultrastructural analysis revealed markedly reduced cell-cell and cell-matrix contacts and loss of cell compaction in all epidermal layers. siRNA-mediated knockdown of SRF in primary human keratinocytes revealed that the cytoskeletal abnormalities and adhesion defects were a direct consequence of the loss of SRF. In contrast, the hyperproliferation observed in vivo was an indirect effect that was most likely a consequence of the inflammation. These results reveal that loss of SRF disrupts epidermal homeostasis and strongly suggest its involvement in the pathogenesis of hyperproliferative skin diseases, including psoriasis. |
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Authors:
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Heidi Koegel; Lukas von Tobel; Matthias Schäfer; Siegfried Alberti; Elisabeth Kremmer; Cornelia Mauch; Daniel Hohl; Xiao-Jing Wang; Hans-Dietmar Beer; Wilhelm Bloch; Alfred Nordheim; Sabine Werner |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-23 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 119 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-02 Completed Date: 2009-04-24 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 899-910 Citation Subset: AIM; IM |
Affiliation:
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Institute of Cell Biology, Department of Biology, ETH Zürich, Zürich, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism Animals Base Sequence Cell Adhesion Cell Differentiation Cell Movement Cell Proliferation Cells, Cultured DNA Primers / genetics Desmosomes / pathology Down-Regulation Female Humans Keratinocytes / metabolism*, pathology* Mice Mice, Mutant Strains Mice, Transgenic Pregnancy Psoriasis / genetics, metabolism, pathology RNA, Small Interfering / genetics Serum Response Factor / antagonists & inhibitors, deficiency*, genetics* Skin / injuries, metabolism, pathology Skin Diseases / genetics, metabolism*, pathology* Wound Healing / genetics, physiology |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/DNA Primers; 0/RNA, Small Interfering; 0/SRF protein, human; 0/Serum Response Factor |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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