Functional analyses of type VII collagen driven from keratinocytes for hair follicles

• Project/Area Number: 20K08665
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Hirosaki University
• Principal Investigator: Matsuzaki Yasushi 弘前大学, 医学部附属病院, 講師 (50322946)
• Co-Investigator(Kenkyū-buntansha): 澤村 大輔 弘前大学, 医学研究科, 教授 (60196334)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: type VII collagen / keratinocyte / 表皮水疱症 / VII型コラーゲン / 表皮細胞

Outline of Research at the Start

栄養障害型表皮水疱症は、COL7A1遺伝子変異のため水疱が生じる先天性皮膚疾患である。
VII型コラーゲン(COLVII) を欠損させたマウスは生下時より水疱が生じ短命である。
COLVIIは主に表皮細胞と線維芽細胞から産生されるが、表皮細胞でのみCOLVII発現を欠損させると、水疱形成は見られず生後20週から顕著な脱毛が出現する。マウスの発毛維持には、表皮細胞由来COLVIIが必須なのか線維芽細胞からのCOLVIIだけでは量的に不十分なのかを解明する。

Outline of Final Research Achievements

We confirmed that NC2-cKO mice, which the expression of NC2 domain is abolished in keratinocytes, showed gradually gray hair and hair loss around 20 weeks old. On the dorsum skin of NC2-cKO mice, normal hair follicles disappeared. Furthermore, the number of sebaceous glands decreased. We successfully established mesenchymal stem cells driven from fat tissues of normal mice. We injected these cells around skin graft from NC2-cKO mice on the Rag2 mice every week. Unfortunately, mesenchymal stem cells did not show the induction of hair growth.

Academic Significance and Societal Importance of the Research Achievements

COLVIIが互いに結合し最終的に三重らせん構造を呈するためには、NC2領域での結合が重要である。COLVIIが関わる脱毛を解析することは毛髪老化現象による壮年性脱毛、頭髪の白毛化の発生機序解明につながると考える。本研究は、COLVII欠損の表皮水疱症患者へ新規COLVIIを提供する基盤となる研究課題であり、また脱毛・白毛化の改善という一般社会にも研究成果が波及することが期待できる創造性をもった研究である。

Research Products

• [Journal Article] A case of COVID‐19 with pernio‐like skin lesions and increased red blood cell distribution width (2022)
  • Author(s): Minakawa Satoko、Matsuzaki Yasushi、Terada Akari、Ogasawara Shu、Nishiya Yuki、Irie Jin、Ishizawa Yoshiya、Hanada Hiroyuki、Sawamura Daisuke
  • Journal Title: Journal of Cutaneous Immunology and Allergy Volume: 6 Issue: 2 Pages: 55-56
  • DOI: 10.1002/cia2.12272
  • Peer Reviewed / Open Access
• [Journal Article] Ultraviolet B irradiation leads to the development of experimental bullous pemphigoid targeting BPAG1e (2022)
  • Author(s): Kogawa Kazuhito、Matsuzaki Yasushi、Kimura Atsuko、Minakawa Satoko、Nakano Hajime、Ito Koichi、Kijima Hiroshi、Sawamura Daisuke
  • Journal Title: Journal of Dermatological Science Volume: 108 Issue: 2 Pages: 112-115
  • DOI: 10.1016/j.jdermsci.2022.12.001
  • Peer Reviewed / Open Access
• [Journal Article] Correlation between lactate dehydrogenase and other laboratory data in patients with atopic dermatitis (2022)
  • Author(s): Kogawa Kazuhito、Minakawa Satoko、Matsuzaki Yasushi、Okamoto Asumi、Ogasawara Shu、Saito Norihiro、Sawamura Daisuke
  • Journal Title: Journal of Cutaneous Immunology and Allergy Volume: - Issue: 4 Pages: 133-135
  • DOI: 10.1002/cia2.12225
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced β-adrenergic response in mice with dominant-negative expression of the PKD2L1 channel. (2022)
  • Author(s): Murakami M, Murakami AM, Nemoto T, Ohba T, Yonekura M, Toyama Y, Tomita H, Matsuzaki Y, Sawamura D, Hirota K, Itagaki S, Asada Y, Miyoshi I.
  • Journal Title: PLoS One Volume: 17 Issue: 1 Pages: 0261668-0261668
  • DOI: 10.1371/journal.pone.0261668
  • Peer Reviewed / Open Access
• [Journal Article] 抗BP230抗体の病原性 (2022)
  • Author(s): 松﨑康司
  • Journal Title: 皮膚科, 2(2):180-7, 2022 Volume: 2 Pages: 180-187
• [Journal Article] Attenuated β-adrenergic response in calcium/calmodulin-dependent protein kinase IV-knockout mice (2021)
  • Author(s): Murakami Manabu、Murakami Agnieszka M.、Matsuzaki Yasushi、Sawamura Daisuke、Ohba Takayoshi、Miyoshi Ichirou、Itagaki Shirou、Sakagami Hiroyuki
  • Journal Title: PLOS ONE Volume: 16 Issue: 4 Pages: 0249932-0249932
  • DOI: 10.1371/journal.pone.0249932
  • Peer Reviewed / Open Access
• [Journal Article] Autoantibodies to BPAG1e Trigger Experimental Bullous Pemphigoid in Mice. (2021)
  • Author(s): Makita Eiko, Matsuzaki Yasushi, Fukui Tomohisa, Matsui Akinobu, Minakawa Satoko, Nakano Hajime, Ito Koichi Kijima Hiroshi, Sawamura Daisuke
  • Journal Title: The Journal of Investigative Dermatology Volume: 4 Issue: 5 Pages: 1167-1176
  • DOI: 10.1016/j.jid.2020.08.031
  • Peer Reviewed / Open Access
• [Journal Article] A Case of Possible Concurrence of Dermatitis Herpetiformis and Linear Immunoglobulin A / Immunoglobulin G Bullous Dermatosis. (2021)
  • Author(s): Minakawa S, Matsuzaki Y, Hashimoto T, Ishii N, Nishie W, Sawamura D.
  • Journal Title: Acta Dermatovenerol Croat. Volume: 29 Pages: 116-117
  • Peer Reviewed
• [Journal Article] Atypical eosinophilic annular erythema clinically resembling granuloma annulare (2021)
  • Author(s): Matsuzaki Yasushi、Minakawa Satoko、Sagara Chihiro、Matsui Akinobu、Nakano Hajime、Sawamura Daisuke
  • Journal Title: International Journal of Dermatology Volume: 60 Issue: 10
  • DOI: 10.1111/ijd.15591
  • Peer Reviewed / Open Access
• [Journal Article] Hidradenitis suppurativa with perifolliculitis capitis abscedens et suffodiens successfully treated with a human anti‐tumour necrosis factor monoclonal antibody (2021)
  • Author(s): Minakawa S.、Matsuzaki Y.、Rokunohe D.、Kumagai N.、Kurose A.、Kushibiki M.、Kayaba H.、Sawamura D.
  • Journal Title: Clinical and Experimental Dermatology Volume: 46 Issue: 8 Pages: 1586-1588
  • DOI: 10.1111/ced.14789
  • Peer Reviewed
• [Journal Article] Current status of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus isolated from patients with skin and soft tissue infections in Japan (2020)
  • Author(s): Nakaminami Hidemasa、Ozawa Kazuya、Sasai Nao、Ikeda Masami、Nemoto Osamu、Baba Naoko、Matsuzaki Yasushi、Sawamura Daisuke、Shimoe Fumiko、Inaba Yoichi、Kobayashi Yoko、Kawasaki Satoru、Ueki Toru、Funatsu Sakae、Shirahama Shigeho、Noguchi Norihisa
  • Journal Title: The Journal of Dermatology Volume: 47 Issue: 11 Pages: 1280-1286
  • DOI: 10.1111/1346-8138.15506
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of the mechanism underlying a mild phenotype of hereditary coproporphyria due to a homozygous missense mutation in the transcription initiation codon of the coproporphyrinogen III oxidase gene (2020)
  • Author(s): Fukui Tomohisa、Akasaka Eijiro、Rokunohe Daiki、Matsuzaki Yasushi、Sawamura Daisuke、Kabashima Kenji、Nakano Hajime
  • Journal Title: Journal of Dermatological Science Volume: 100 Issue: 2 Pages: 156-159
  • DOI: 10.1016/j.jdermsci.2020.06.006
  • Peer Reviewed
• [Journal Article] Decreased cardiac pacemaking and attenuated beta-adrenergic response in TRIC-A knockout mice. (2020)
  • Author(s): Murakami M, Toyama Y, Yonekura M, Ohba T, Matsuzaki Y, Sawamura D, Murakami AM, Nishi M, Itagaki S, Tomita H, Takeshima H.
  • Journal Title: Plos ONE Volume: 15 Issue: 12 Pages: 1-12
  • DOI: 10.1371/journal.pone.0244254
  • Peer Reviewed / Open Access
• [Presentation] Correlation between lactate dehydrogenase and total IgE levels, TARC levels, and eosinophil count in patients with atopic dermatitis (2023)
  • Author(s): S Minakawa, K Kogawa, Y Matsuzaki, A Okamoto, S Ogasawara, N Saito, D Sawamura.
  • Organizer: 81st Annual Meeting of the American Academy of Dermatology
  • Int'l Joint Research
• [Presentation] Possible correlation of serum anti-BP180-NC16a antibody and thymus and activation-regulated chemokine in patients with bullous pemphigoid. (2023)
  • Author(s): S Minakawa, Y Matsuzaki, D Sawamura.
  • Organizer: 81st Annual Meeting of the American Academy of Dermatology
  • Int'l Joint Research
• [Presentation] 水痘を発症した皮膚筋炎の1例 (2022)
  • Author(s): 皆川 智子、松崎 康司、山下 あや、六戸 亜希子、中野 創、澤村 大輔、平賀 寛人
  • Organizer: 日本皮膚科青森地方会第400回例会
• [Presentation] 腎移植患者に生じた隆起性皮膚線維肉腫 (2022)
  • Author(s): 古川 和仁、六戸 大樹、山下 あや、赤坂 英二郎、中島 康爾、松崎 康司、中野 創、澤村 大輔、原 憲司、小野 彩
  • Organizer: 日本皮膚科学会青森地方会第399回例会
• [Presentation] 水疱性類天疱瘡における抗BP230抗体の病原性 (2022)
  • Author(s): 松﨑康司
  • Organizer: 第121回日本皮膚科学会総会
  • Invited