Elucidation of abnormal calcium signal response in keloid-derived fibroblasts to stretch stimuli

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10009
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: The University of Tokushima
• Principal Investigator: MINEDA Kazuhide 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (70747815)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ケロイド / 線維芽細胞 / カルシウムイオン濃度 / カルシウムシグナル応答

Outline of Final Research Achievements

Using our original cell stretching device, we observed intracellular Ca2+ levels in keloid-derived fibroblasts(K-FBs) and normal skin-derived fibroblasts(N-FBs) in real time while repeatedly applying stretch stimuli, and found a specific subpopulation (approximately 10%) in K-FBs with pathologically elevated intracellular Ca2+ levels. Ca oscillations were also frequently observed.
Single Cell RNA-seq analysis revealed that the number of cells expressing TRPV2(Ca2+ channel) was significantly higher in K-FBs(11.5% vs. 2.3%) than in N-FBs (approximately 10%). In addition, all Keloid-TRPV2(+) were α-SMA(+), suggesting that the keloid-specific subpopulation was TRPV2(+) myofibroblasts.

Free Research Field

形成外科

Academic Significance and Societal Importance of the Research Achievements

ケロイドは、縫合創、外傷や熱傷による創傷、ニキビなどの軽微な傷から発症する。赤く盛り上がり、病変部を超えて拡大し、痛みやかゆみを伴い、整容的に悩まれることも多い。
様々な治療法が存在するが、第1選択は未だステロイド剤であり、長期投与すると表皮の菲薄化や皮下脂肪の萎縮などの副作用を生じる。本研究課題で解明したケロイド特異的亜集団と想定されたTRPV2(+)の筋線維芽細胞に対するTRPV2の抑制剤が、ステロイド剤に代わる治療薬に成り得るか検証を進めている。