Contribution of stiffness of extracellular matrix to pathogenesis of keloid

• Project/Area Number: 26670777
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Plastic surgery
• Research Institution: Jichi Medical University
• Principal Investigator: Sarukawa Shunji 自治医科大学, 医学部, 講師 (90324194)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: メカノトランスダクション / ケロイド

Outline of Final Research Achievements

① We assayed subcellular localization of YAP, which was recently identified as a sensor and a mediator of mechanical signals, in human dermal fibroblasts grown on collagen-type 1 coated-hydrogels on varying stiffness, and confirmed YAP was nuclear on hard substrates but became predominantly cytoplasmic on soft substrates.
② We identified nuclear translocation of YAP in human keloids but not normal white scars and nomad skins with immunohistochemical staining.
③ Gene expressions of extracellular matrix on hard substrates were higher in keloid-derived fibroblasts than white scar-derived fibroblasts and normal skin-derived fibroblasts.