Soluble Form of Heparin-binding EGF-like Growth Factor Contributes to Retinoic Acid-induced Epidermal Hyperplasia
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- Kimura Rina
- Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University New address: Department of Etiology and Pathogenesis, National Cardiovascular Center
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- Iwamoto Ryo
- Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University
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- Mekada Eisuke
- Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University
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Heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF-family, is thought to be important for keratinocyte functions. HB-EGF is first synthesized as a membrane-anchored form, and its soluble form is released by ectodomain shedding. Here we investigate the role of HB-EGF in epidermal hyperplasia induced by all-trans retinoic acid (tRA) treatment. HB-EGF is normally expressed in epidermis of normal adult mice at very low levels, but topical tRA treatment results in epidermal hyperplasia, concomitant with the strong induction of HB-EGF expression in the suprabasal layer. tRA-induced epidermal hyperplasia was reduced both in the keratinocyte-specific HB-EGF null mice (K5-HBdel/del) and knock-in mice expressing the uncleavable mutant form of HB-EGF (HBuc/uc), as compared with wild-type HB-EGF knock-in mice (HBlox/lox). Among ErbB tyrosine kinase receptors, EGF receptor (EGFR) and ErbB2 were selectively activated by tRA treatment in skin from wild-type mice, while the activation of these ErbB receptors was significantly reduced in the skin of HB-EGF null mice. These results indicate that expression of HB-EGF and generation of its soluble form, followed by activation of EGFR and ErbB2, are pivotal processes in tRA-induced epidermal hyperplasia.<br>
収録刊行物
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- Cell Structure and Function
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Cell Structure and Function 30 (2), 35-42, 2005
日本細胞生物学会
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詳細情報 詳細情報について
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- CRID
- 1390282679672173824
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- NII論文ID
- 40007227358
- 130004137496
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- NII書誌ID
- AA0060007X
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- ISSN
- 13473700
- 03867196
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- NDL書誌ID
- 7889102
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
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- KAKEN
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- 使用不可