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Analysis of the role of Stat3 in protecting apoptosis in skin

Research Project

Project/Area Number 13670885
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SANO Shigetoshi  Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (80273621)

Co-Investigator(Kenkyū-buntansha) KIRA Masahiro  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90314335)
OZAWA Kentarou  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50301255)
ITAMI Satoshi  Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (30136791)
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: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsStat3 / apoptosis / epidermal keratinocyte / Bcl-xL / signaling / ultraviolet irradiation / knockout mouse / skin cancer / 組織特異的遺伝子破壊法 / 紫外線 / 毛包成長 / 創傷治療 / BCL-XL / BCP-XL
Research Abstract

Stat3 functions not only as an intracellular signaling molecule but as an anti-apoptotic molecule. To elucldate the role of Stat3 in the epidermis, we generated keratinocyte-speclflc Stat3 knockout mice by using the Cre/loxP system. The mutant mice were born normal in gross without alteration in the morphogenesis of skin and appendages such as hair follicles. However, they exhibited a delay in wound healing, and failure in entering of the second hair cycle. In vitro cell migration assay of Stat3-deficlent keratinocytes revealed that Stat3 is required for growth factor-dependent cell motility, although cell proliferation was not affected. We concluded that Stat3 of keratinocytes is essential for wound healing and hair cycle through transmission of signals for cell migration. Furthermore, Stat3 knockout mice generated more sunburn cells, that represent apoptotic keratinocytes in the epidermis, than wild-type mice by ultraviolet (UV) B irradiation. This result suggested that Stat3 plays an anti-apoptotic role against UV stress. It has been reported that Stat3 exert an anti-apoptotic effect through transcriptional upregulation of Bcl-xL, a member of BCL-2 family. We established keratinocyte-specific BcI-xL mice using the Cre/loxP, because Bcl-x gene targeting in the gerniline resulted in embryonic lethality so as found in Stat3 gene targeting. Bcl-xL-deficlent mice were born normal and devoid of gross change in skin and appendages. However, we found that they demonstrated many apoptotic keratinocytes in the epidermis, suggesting that Bcl-xL is required for keratinocyte survival. Since it is known that activated Stat3 and enhanced expression of Bcl-xL are associated with many cancer and sarcomas. We are now under investigation, by using knockout mice, on the relation between cancer development and these anti-apoptotic molecules.

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Sano S, Itami S, Takeda K, Tarutani M, Yamaguchi Y, Miura H, Yoshikawa K, Akira S, Takeda J.: "Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis"EMBO J. 18. 4657-4668 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sano S, Kira M, Takagi S, Yoshikawa K, Takeda J, Itami S.: "Two distinct signaling pathways in hair cycle inducation : Stat3 -dependent and -independent pathways"Proc Natl Acad Sci USA. 97. 13824-13829 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sano S, Takahama Y, Sugawara T, Kosaka H, Itami S, Yoshikawa K, Miyazki J-I, van Ewijk W, Takeda J.: "Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic architecture and thymocyte survival"Immunity. 15. 261-273 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sano S, Takeda J, Yoshikawa K, Itami S.: "Tissue regeneration : hair follicle as a model"J Invest Dermatol Proceedings. 6. 43-48 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kira M, Sano S, Takagi S, Yoshikawa K, Takeda J, Itami S.: "Stat3 deficiency in keratinocytes leads to compromised cell migration through hyperphosphorylation of P130 cas"J Biol Chem. 277. 12931-12936 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jiro Umeda, Shigetoshi Sano, Kazuhiko Kogawa, Noboru Motoyama, Kunihiko Yoshikawa, Satoshi Itami, Gen Kondoh, Takeshi Watanabe, Junji Takeda.: "In vivo cooperation between Bcl-xL and the phosphoinositide 3 -kinase-Akt signaling pathway for the protection of epidermal keratinocytes from apoptosis"FASEB J. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sano S, Itami S, Takeda K, Tarutani M, Yamaguchi Y, Miura H, Yoshikawa K, Akira S, Takeda J.: "Keratinocyte-speciflc ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis."EMBO J.. 18. 4657-68 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sano S, Kira M, Takagi S, Yoshikawa K, Takeda J, Itami S.: "Two distinct signaling pathways in hair cycle inducation : Stat3 - dependent and - independent pathways."Proc Natl Acad Sci USA. 97. 13824-13829 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sano S, Takahama Y, Sugawara T, Kosaka H, Itami S, Yoshikawa K, Miyazki J-l, van Ewijk W, Takada J.: "Stat3 in thymic eplthellal cells is esseatlal for postnatal maintenance of thymic architecture and thymocyte survival."Immunity.. 15. 261-273 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sano S, Takeda J, Yoshikawa K, Itami S.: "Tissue regeneration : hair follicle as a model"J Invest Dermatol Proceedings. 6. 43-48 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kira M, Sano S, Takagi S, Yoshikawa K, Takeda J, Itami S.: "Stat3 detlclency in keratinocytes leads to compromised cell migration through hyperphosphorylation of P130 cas."J Biol Chem.. 277. 12931-12936 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jiro Umeda, Shigetoshi Sano, Kazuhiko Kogawa, Noboru Motoyama, Kunihiko Yoshikawa, Satoshi Itami, Gen Kondoh, Takeshi Watanabe, Junji Takeda.: "In vivo cooperation between Bcl-xL and the phosphoinositlde 3-kinase-Akt siguailing pathway far the protection of epidermal keratinocytes from apoptosis."FASEB J.. (In press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sano S, Itami S, Takeda K, Tarutani M, Yamaguchi Y, Miura H, Yoshikawa K, Akira S, Takeda J.: "Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis"EMBO J. 18. 4657-4668 (1999)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sano S, Kira M, Takagi S, Yoshikawa K, Takeda J, Itami S.: "Two distinct signaling pathways in hair cycle inducation : Stat3 -dependent and -independent pathways"Proc Nail Acad Sci USA. 97. 13824-13829 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sano S, Takahama Y, Sugawara T, Kosaka H, Itami S, Yoshikawa K, Miyazki J-I, van Ewijk W, Takeda J.: "Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic architecture and thymocyte survival"Immunity. 15. 261-273 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sano S, Takeda J, Yoshikawa K, Itami S.: "Tissue regeneration : hair follicle as a model"J Invest Dermatol Proceedings. 6. 43-48 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kira M, Sano S, Takagi S, Yoshikawa K, Takeda J, Itami S.: "Stat3 deficiency in keratinocytes leads to compromised cell migration through hyperphosphory lation of P130cas"J Biol Chem. 277. 12931-12936 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Jiro Umeda, Shigetoshi Sano, Kasuhiko Kogawa, Noboru Motoyama, Kunihiko Yoshikawa, Satoshi Itami, Gen Kondoh, Takeshi Watanabe, Junji Takeda: "In vivo cooperation between Bcl_XL and the phosphoinositide 3-kinase-Akt signaling pathway for the protection of epidermal keratinocytes from apoptosis"FASEB J. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sano S, Itami S, Takeda K, Tarutani M, Yamaguchi Y, Miura H, Yoshikawa K, Akira S, Takeda J: "Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis"EMBO J. 18. 4657-4668 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sano S, Kira M, Takagi S, Yoshikawa K, Takeda J, Itami S: "Two distinct signaling pathways in hair cycle inducation : Stat3-dependent and-independent pathways"Proc Natl Acad Aci USA. 97. 13824-13829 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sano S, Takahama Y, Sugawara T, Kosaka H, Itami S, Yoshikawa K, Miyazki J-l, van Ewijik W, Takeda J: "Stat3 in thymic epithelial cell is essential for postnatal maintenance of thymic architecture and thymocyte survival"Immunity. 15. 261-273 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sano S, Takeda J, Yoshikawa K, Itami S: "Tissue regeneration : hair follicle as a model"J Invest Dermatol Proceedings. 6. 43-48 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kira M, Sano S, Takagi S, Yoshikawa K, Takeda J, Itami S: "Stat3 deficiency in keratinocytes leads to compromised cell migration through hyperphosphorylation of P130 cas."J Biol Chem. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 佐野 栄紀: "毛包とSTAT3"臨床皮膚科. 55・53. (2001)

    • Related Report
      2001 Annual Research Report

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

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