Possible involvement of NEDD4 in keloid formation; its critical role in fibroblast proliferation and collagen production

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概要

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• Keloid represents overgrowth of granulation tissue, which is characterized by collection of atypical fibroblasts with excessive deposition of extracellular matrix components, after skin injury, but its etiology is still largely unknown. We recently performed genome-wide association study (GWAS) of keloid and identified NEDD4 to be one of candidate molecules associated with keloid susceptibility. Here we demonstrate a possible mechanism of NEDD4 involvement in keloid formation through enhancement of the proliferation and invasiveness of fibroblasts as well as upregulation of type 1 collagen expression. Activation of NEDD4 affected subcellular localization and protein stability of p27 which was implied its critical role in contact inhibition. It also induced accumulation of β-catenin in the cytoplasm and activated the TCF/β-catenin transcriptional activity. Furthermore, NEDD4 upregulated expressions of fibronectin and type 1 collagen and contributed to the excessive accumulation of extracellular matrix. Our findings provide new insights into mechanism developing keloid and can be applied for development of a novel treatment for keloid.(Communicated by Kumao TOYOSHIMA, M.J.A.)

• 日本学士院の論文

著者

• Chung Suyoun

  Laboratory Of Molecular Medicine Human Genome Center Institute Of Medical Science The University Of

• Zembutsu Hitoshi

  Laboratory Of Molecular Medicine Human Genome Center Institute Of Medical Science The University Of

• Nakamura Yusuke

  Laboratory For Genotyping Riken Snp Research Center C/o Riken Yokohama Institute

• NAKASHIMA Mitsuko

  Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University

• CHUNG Suyoun

  Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo

• ZEMBUTSU Hitoshi

  Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo

• NAKASHIMA Mitsuko

  Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo

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