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Role of keratinocyte apoptosis and differentiation regulated by ASK1 in wound healing

Research Project

Project/Area Number 13670889
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionEhime University

Principal Investigator

SAYAMA Koji  Ehime University Faculty of Medicine, Associate Professor, 医学部, 助教授 (80187286)

Co-Investigator(Kenkyū-buntansha) YAMASAKI Kenshi  Ehime University. Faculty of Medicine, Instructor, 医学部, 助手 (40294798)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsskin / wound healing / differentiation / ASK1 / MAP kinase / PI3 kinase / bacteria / apoptosis / p38MAP kinase / 表皮 / 角化細胞 / トランスジェニック
Research Abstract

Apoptosis and differentiation of epidermal keratinocyte play an important role in skin wound healing. Since, ASK1 regulates apoptosis and differentiation of keratinocyte, ASK1 may regulate skin wound healing. In addition to ASK1, PI3 kinase, which also regulates apoptosis, may contributes skin wound healing. After damage of the cultured human keratinoycte, JNK and p38 MAP kinase activity was analyzed. The damage activated the JNK and p38 MAP kinase, suggesting the activation of ASK1-JNK, and -p38 MAP kinase cascades. Bacterial infection retards skin wound healing. The effect of bacterial infection on keratinocyte was analyzed. Contact of bacteria to cultured keratinocyte induced the production of anti-microbacterial peptides. Next we analyzed whether PI3 kinase regulate keratinoycte differentiation. Differentiation induced the expression of K1 and K10 mRNA. This induction was reduced by expression of active PI3 kinase, indicating that PI3 kinase regulates skin wound healing by apoptosis and differentiation. After formation of wound on the back of mouse, the process of wound healing was histological observed.
Keratinocyte apoptosis was detected with TUNEL method on the surrounding skin. Immunohistochemical staining showed that the expression of ASK1 on the epidermal keratinocytes. In conclusion, ASK1 plays an important role in skin wound healing by regulating apoptosis and differentiation of epidermal keratinoycte.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Yamasaki K, Hanakawa Y, Tokumaru S, Shirakata Y, Sayama K, Hanada T, Yoshimura A, Hashimoto K: "SOCS1/JAB and SOCS3/CIS3 negatively regulate the STATs signaling pathway in normal human epidermal keratinocytes. J Invest Dermatol, (in press)"J Invest Dermatol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamasaki K, Toriu N, Hanakawa Y, Shirakata Y, Sayama K, Takayanagi A, Ohtsubo M, Gamou S, Shimizu N, Fujii M, Miyazono K, Hashimoto K: "Keratinocyte growth inhibition by high-dose epidermal growth factor is mediated by transforming growth factor autoinduction : A negative feedback mechanism for keratinocyte growth"J Invest Dermatol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuda T, Thoyama M, Yamasaki K, Shirakata Y, Yahata Y, Tokumaru S, Sayama K, Hashimoto K: "Lack of evidence for TARC/CCL17 production by normal human keratinocytes in vitro"J Dermatol Sci. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shirakata Y, Tamai K, Nakaoka H, Tokumaru S, Sayama K, Murakami S, Hashimoto K: "Severe Palmo-plantar Hyperkeratosis in Koebner Epidermolysis Bullosa Simplex"J Dermatol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yanai F, Ishii E, Kojima K, Hasegawa A, Azuma T, Hirose S, Suga N, Mitsudome A, Zaitsu M, Ishida Y, Shirakata Y, Sayama K, Hashimoto K, Yasukawa M: "Essential roles of perforin in antigen-specific cytotoxicity mediated by human CD4+ T lymphocytes : analysis using the combination of hereditary perforin-deficient effector cells and Fas-deficient target cells"J Immunol.. 170(4). 2205-2213 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ii M, Sayama K, Tohyama M, Hashimoto K.: "A case of cold-dependent exercise-induced anaphylaxis"Br J Dermatol.. 147(2). 368-370 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sayama K, Yamasaki K, Hanakawa Y, Shirakata Y, Tokumaru S, Ijuin T, Takenawa T, Hashimoto K: "Phosphatidyl inositol 3 kinase is a key regulator of early phase differentiation in keratinocytes"Biol Chem. 277. 40390-40396 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hanakawa Y, Amagai M, Shirakata Y, Yahata Y, Tokumaru S, Yamasaki K, Tohyama M, Sayama K, Hashimoto K: "Differentiatl effects of desmoglein 1 and desmoglein 3 on desmosome formation"J Invest Dermatol. 119. 1231-1236 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohyama M, Shirakara Y, Yamasaki K, Sayama K, Hashimoto K: "Differentiated keratinocytes are responsible for TNF-alpha regulated production of macrophage inflammatory protein 3alpha/CCL20, a potent chemokine for Langerhans cells"J Dermatol Sci. 27(2). 130-139 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sayama K, Hanakawa Y, Shirakata Y, Yamasaki K, Sawada Y, Sun L, Yamanishi K, Ichijo H, Hashimoto K K: "Apoptosis signal regulating kinase 1 (ASK1) is an intracellular inducer of keratinocyte differentiation. J Biol Chem 276:999-1004, 2001"J Biol Chem. 276. 999-1004 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamasaki K, Hanakawa Y, Tokumaru S, Shairakata Y, Sayama K, Hanada T, Yoshimura A, Hashimoto K: "SOCS1/JAB and SOCS3/CIS negatively rgulate the STATs signaling pathway in normal human epidermal keratinocytes"J Invest. Dermatol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamasaki K, Toriu N, Hanakawa Y, Shirakata Y, Sayama K, Takayanagi A, Ohtsubo M, Gamou S, Shimizu N, Fujii M, Miyazono K, Hashimoto K: "Keratinocyte growth inhibition by high-dose epidermal growth factor is mediated by transforming growth factor autoinduction : A negative feedback mechanism for keratinocyte growth"J Invest. Dermatol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuda T, Thoyama M, Yamasaki K, Shirakata Y, Yahata Y, Tokumaru S, Sayama K, Hashimoto K: "Lack of evidence for TARC/CCL17 production by Nomal human keratinocytes in vitro"J. Dermatol. Sci.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shirakata Y, Tamai K, Nakaoka H, Tokumaru S, Sayama K, Murakami S, Hashimoto K: "Severe Palmo-plantar hyperkeratosis in koebner epidermolysis bullosa simp"J Dermatol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yanai F, Ishii E, Kojima K, Hasegawa A, Azuma T, Hirose S, Suga N, Mitsudome A, Zaitsu M, Ishida Y, Shirakata Y, Sayama K, Hashimoto K, Yasukawa M.: "Essential roles of perforin in antigen-specific cytotoxicity mediated by human CD4+ T lymphocytes : analysis using the combination of hereditary perforin-deficient effector cells and Fas-deficient target cells"J Immunol.. 170(4). 2205-2213 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ii M, Sayama K, Tohyama M, Hashimoto K.: "A case of cold-dependent exercise-induced anaphylaxis"Br J Dermatol.. 147(2). 368-370 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sayama K, Yamasaki K, Hanakawa Y, Shirakata Y, Tokumaru S, Ijuin T, Takenawa T, Hashimoto K: "Phosphatidyl inositol 3 kinase is a key regulator of early phase differentiation in keratinocytes"J Biol Chem.. 277. 40390-40396 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hanakawa Y, Amagai M, Shirakata Y, Yahata Y, Tokumaru S, Yamasaki K, Tohyama M, Sayama K, Hashimoto K: "Differentiatl effects of desmoglein 1 and desmoglein 3 on desmosome formation"J Invest Dermatol.. 119. 1231-1236 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohyama M, Shirakara Y, Yamasaki K, Sayama K, Hashimoto K.: "Differentiated keratinocytes are responsible for TNF-alpha regulated production of macrophage inflammatory protein 3alpha/CCL20, a potent chemokine for Langerhans cells"J Dermatol Sci.. 27(2). 130-139 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sayama K, Hanakawa Y, Shirakata Y, Yamasaki K, Sawada Y, Sun L, Yamanishi K, Ichijo H, Hashimoto K: "Apoptosis signal regulating kinase 1 (ASK1) is an intracellular inducer of keratinocyte differentiation"J Biol Chem.. 276. 999-1004 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamasaki, K., Hanakawa, Y., Tokumaru, S., Shirakata, Y., Sayama, K., Hanada, T., Yoshirnura, A., Hashimoto, K: "SOCS1/JAB and SOCS3/CTS3 negatively regulate the STATs signaling pathway in normal human epidermal keratinocytes."J Invest Dermatol. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamasaki, K., Toriu, N., Hanakawa, Y., Shirakata, Y., Sayama, K., Takayanagi, A., Ohtsubo, M., Garnon, S., Shimizu, N., Fujii, M., Miyazono, K., Hashimoto, K.: "Keratinocyte growth inhibition by high-dose epidermal growth factor is mediated by transforming growth factor autoinduction : A negative feedback mechanism for keratinocyte growth"J Invest Dermatol. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuda, T., Thoyarna, M., Yamasaki, K., Shirakata, Y., Yahata, Y., Tokumaru, S., Sayama, K., Hashimoto, K.: "Lack of evidence for TARC/CCL17 production by normal human keratinocytes in vitro."J Dermatol Sci. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Shirakata, Y., Tamai, K., Nakaoka, H., Tokumaru, S., Sayama, K., Murakami, S., Hashimoto, K.: "Severe Palmo-plantar Hyperkeratosis in Koebner Epidermolysis Bullosa Simplex."J Dermatol. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yanai, F., Ishii, E., Kojima, K., Hasegawa, A., Azuma, T., Hirose, S., Suga, N., Mitsudome, A., Zaitsu, M., Ishida, Y., Shirakata, Y., Sayama, K., Hashimoto, K., Yasukawa, M.: "Essential roles of perforin in antigen-specific cytotoxicity mediated by human CD4+ Tlymphocytes : analysis using the combination of hereditary perforin-deficient effector cells and Fas-deficient target cells."J Immunol.. 170(4). 2205-2213 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ii, M., Sayama, K., Tohyama.M., Hashirnoto, K..: "A case of cold-dependent exercise-induced anaphylaxis."Br J Dermatol.. 147(2). 368-370 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sayama, K., Yamasaki, K., Hanakawa, Y., Shirakata, Y., Tokumaru, S., Ijuin, T., Takenawa, T., Hashimoto, K.: "Phosphatidyl inositol 3 kinase is a key regulator of early phase differentiation in keratinocytes."Biol Chem. 277. 40390-40396 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Tohyama: "Re1A-associated Inhibitor (RA1) Regulates NP-κB in Differentiated Keratinocytes"J. Invest. Dermatol.. 117. 407 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Sayama: "Phsphatidylinositol 3-Kinase(PI3K) Regulates Early Phase Keratinocyte Differentiation"J. Invest. Dermatol. 117. 408 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Yamasaki: "Keratinocyte Growth Inhibition by High Doses of Epidermal Growth Factor is Mediated Through Autoinduction of Transforming Growth Factor β: A Negative Feedback Mechanism of Keratinocyte Growth"J. Invest. Dermal. 117. 478 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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