Journal
PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES
Volume 87, Issue 8, Pages 563-573Publisher
JAPAN ACAD
DOI: 10.2183/pjab.87.563
Keywords
NEDD4; keloid; contact inhibition; EMT
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Funding
- Ministry of Education, Culture, Sports, Science anti Technology of the Japanese government
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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 gamma-catenin in the cytoplasm and activated the TCF/beta-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.
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