Determination of the functions of specific CD44 proteins in human skin and epidermis and their relation to skin diseases, cancer and autoimmunity

• Project/Area Number: 16K10137
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kurume University
• Principal Investigator: TEYE Kwesi 久留米大学, 付置研究所, 助教 (30599303)
• Co-Investigator(Kenkyū-buntansha): 橋本 隆 久留米大学, 皮膚細胞生物学研究所, 教授 (20129597) ; 名嘉真 武国 久留米大学, 医学部, 教授 (50221453) ; 沼田 早苗 久留米大学, 医学部, 助教 (40599312) ; 石井 文人 久留米大学, 医学部, 准教授 (80330827)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: CD44 / Skin / Skin disease / Keratinocyte / Squamous cell carcinoma / migration / Human Skin Keratinocyte / Skin Cancer / Human Skin / 皮膚生理 / 生物学

Outline of Final Research Achievements

We studied functions and roles of CD44 proteins in human skin. We for the first time identified 18 transcripts of CD44 in epidermal keratinocytes and studied their roles in skin development. To gain insight into CD44 function, we performed immunostaining of normal skin and various skin diseases. We found decreased expression of CD44 variants in various skin cancers, particularly squamous cell carcinoma but not in inflammatory diseases psoriasis and atopic dermatitis. Using CRISPR/Cas9 system, we successfully disrupted CD44 expression in keratinocyte cell line and performed Microarray analysis using RNA from cells with and without CD44. We found that expression of many important genes are controlled by CD44. Importantly, we found that expression of all 3 subunits of a certain laminin, which is important for maintaining structural integrity of human skin, are reduced in cells without CD44. Cells without CD44 migrated slower. Our study revealed important functions of CD44 in human skin.

Academic Significance and Societal Importance of the Research Achievements

CD44の皮膚での役割はよく分かっていない。本研究ではCD44の発現が有棘細胞癌で減少していること、CD44の発現をなくした表皮細胞において、皮膚の構造を保つ上で重要な働きをするラミニンの3つのサブユニットの発現がすべて減少していることを明らかにした。またCD44を有さない表皮細胞は移動が遅くなることも明らかにした。以上の結果からCD44は創傷治癒において重要な役割を果たしている可能性が示唆された。CD44はある種の皮膚疾患において、治療の標的になり得るかもしれない。

Research Products

• [Journal Article] Detection of anti‐type VII collagen IgE antibodies in epidermolysis bullosa acquisita (2019)
  • Author(s): Koga H.、Teye K.、Yamashita K.、Ishii N.、Tsuruta D.、Nakama T.
  • Journal Title: British Journal of Dermatology Volume: 180(5) Pages: 1107-1113
  • DOI: 10.1111/bjd.17310
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical and Immunological Study of 30 Cases With Both IgG and IgA Anti-Keratinocyte Cell Surface Autoantibodies Toward the Definition of Intercellular IgG/IgA Dermatosis (2018)
  • Author(s): Hashimoto Takashi、Teye Kwesi、Hashimoto Koji、Wozniak Katarzyna、Ueo Daisuke、Fujiwara Sakuhei、Inafuku Kazuhiro、Kotobuki Yorihisa、Jukic Ines Lakos、Marinovi? Branka、Bruckner Anna、Tsuruta Daisuke、Kawakami Tamihiro、Ishii Norito
  • Journal Title: Frontiers in Immunology Volume: 9 Pages: 994-994
  • DOI: 10.3389/fimmu.2018.00994
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High Index Values of Enzyme-Linked Immunosorbent Assay for BP180 at Baseline Predict Relapse in Patients With Bullous Pemphigoid. (2018)
  • Author(s): Koga H, Teye K, Ishii N, Ohata C, Nakama T
  • Journal Title: Front Med (Lausanne). Volume: 5 Pages: 139-139
  • DOI: 10.3389/fmed.2018.00139
  • Peer Reviewed / Open Access
• [Journal Article] The haptoglobin promoter polymorphism rs5471 is the most definitive genetic determinant of serum haptoglobin level in a Ghanaian population. (2018)
  • Author(s): Soejima M, Teye K, Koda Y.
  • Journal Title: Clinica Chimica Acta Volume: 483 Pages: 303-307
  • DOI: 10.1016/j.cca.2018.05.029
  • Peer Reviewed
• [Journal Article] Multimerization is required for antigen binding activity of an engineered IgM/IgG chimeric antibody recognizing a skin-related antigen (2017)
  • Author(s): Teye K, Hashimoto K, Numata S, Ohta K, Haftek M, Hashimoto T
  • Journal Title: Scientific Reports Volume: 7 Pages: 8212-8212
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Detection of SERPINB7 mutation can distinguish Nagashima-type palmoplantar keratoderma from other keratodermas with palmoplantar lesions (2017)
  • Author(s): Hashimoto T, Teye K, Numata S, Suga Y, Hamada T, Ishii N
  • Journal Title: Clinical and Experimental Dermatology Volume: 42 Pages: 324-325
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prevalence of filaggrin gene mutations in patients with atopic dermatitis and ichthyosis vulgaris in Kyushu area of Japan and South Korea (2017)
  • Author(s): Teye K, Numata S, Krol RP, Ishii N, Matsuda M, Lee JB, Hamada T, Hashimoto T
  • Journal Title: Journal of Dermatological Science Volume: 86 Pages: 174-177
  • Peer Reviewed
• [Journal Article] Detection of IgE autoantibodies to BP180 and BP230 and their relationship to clinical features in bullous pemphigoid (2017)
  • Author(s): Hashimoto T, Ohzono A, Teye K, Numata S, Hiroyasu S, Tsuruta D, Hachiya T, Kuroda K, Hashiguchi M, Kawakami T, Ishii N
  • Journal Title: Br J Dermatology Volume: 177(1) Pages: 141-151
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Isolation of All CD44 Transcripts in Human Epidermis and Regulation of Their Expression by Various Agents. (2016)
  • Author(s): Kwesi Teye, Sanae Numata, Norito Ishii, Rafal P. Krol, Atsunari Tsuchisaka, Takahiro Hamada, Hiroshi Koga, Tadashi Karashima, Chika Ohata, Daisuke Tsuruta, Hideyuki Saya, Marek Haftek, Takashi Hashimoto
  • Journal Title: PLoS ONE Volume: 11(8)
  • DOI: 10.1371/journal.pone.0160952
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Unusual CD44 form in epidermal differentiation. (2019)
  • Author(s): Kwesi Teye, Hiroshi Koga, Norito Ishii, Sanae Numata, Takashi Hashimoto, Marek Haftek, Takekuni Nakama,
  • Organizer: Gordon Research Conference (GRC) on Barrier Function of Mammalian Skin.（Waterville Valley, NH, USA, August 11 - 16, 2019）
  • Int'l Joint Research / Invited
• [Presentation] Filaggrin gene (FLG) promoter polymorphisms are associated with atopic dermatitis but not ichthyosis vulgaris. (2018)
  • Author(s): Kwesi Teye, Hiroshi Koga, Akira Nagai, Chika Ohata, Sanae Numata, Norito Ishii, and Takekuni Nakama.
  • Organizer: 第25回分子皮膚科学フォーラム, Hakodate,（April 13-14, 2018）
• [Presentation] Filaggrin gene (FLG) promoter polymorphisms are associated with atopic dermatitis but not ichthyosis vulgaris in Japan, (2018)
  • Author(s): Kwesi Teye, Hiroshi Koga, Akira Nagai, Chika Ohata, Sanae Numata, Norito Ishii and Takekuni Nakama,
  • Organizer: IID2018, Orlando, Florida,（May 16-19, 2018）
  • Int'l Joint Research
• [Presentation] Multimerization is required for antigen binding activity of an engineered IgM/IgG chimeric antibody recognizing a skin-related antigen (2017)
  • Author(s): Teye K, Hashimoto K, Numata S, Ohta K, Haftek M, Hashimoto T
  • Organizer: 42st Annual Meeting of the Japanese Society for Investigative Dermatology
• [Presentation] Identification of CD44 transcripts that segregate with proliferation, redox and differentiation activities in human keratinocytes. (2016)
  • Author(s): Kwesi Teye, Sanae Numata, Norito Ishii, Koga Hiroshi, Daisuke Tsuruta, Hideyuki Saya, Marek Haftek, Takashi Hashimoto.
  • Organizer: 43rd Annual SCUR Meeting
  • Place of Presentation: Lyon, France.
  • Year and Date: 2016-08-29
  • Int'l Joint Research