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Analysis of the role of keratinocyte Stat3 using the epithelia-specific gene ablation technology.

Research Project

Project/Area Number 11670828
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  Graduate School of Medicine, Osaka University Lecturer, 医学系研究科, 講師 (80273621)

Co-Investigator(Kenkyū-buntansha) YOSHIKAWA Kunihiko  Graduate School of Medicine, Osaka University Professor, 医学系研究科, 教授 (20110851)
ITAMI Satoshi  Graduate School of Medicine, Osaka University Associate Professor, 医学系研究科, 助教授 (30136791)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsepidermal keratinocyte / Stat3 / Signal transduction / growth factor / migration / wound healing / hair cycle / ulcer formation
Research Abstract

We have established keratinocyte-specific Stat3-disrupted mice by using Cre-loxP system under the keratin 5 promoter in order to Investigate the role of Stat3 in signaling required within keratinocytes, since germline ablation of Stat3 gene resulted in early embryonic lethality. Although Stat3-disrupted mice were born normal and no alteration in the skin was found, It was found that wound healing was greatly retarded and the second hair cycle was absent. In vitro migration assay revealed that growth factor-mediated cell migration was markedly impaired in Stat3-disrupted keratinocytes, while their proliferative responses were Intact. These results indicated that Stat3 in keratinocytes was dispensable for skin morphogenesis, but essential for the skin remodeling including wound healing and the progression of the second hair cycle, the processes which required keratinocyte migration. Interestingly, anagen of Stat3- disrupted mice was Induced by topical application of PMA or hair plucking compared to control mice. Furthermore, we found that Stat3-disrupted keratinocytes migrated in vitro upon PKC activation. Given that anagen process required keratinocyte migration, these results suggested that there were at least two distinct pathways for anagen progression based on keratinocyte migration, Stat3-dependent and independent pathways. Interestingly, both signal pathways required PI3K activation. Thus we elucidated signaling pathways and their crosstalks that are Involved in hair cycling using keratinocyte-specific Stat3-disrupted mice.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 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)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeda J,Sano S,Tarutani M,Umeda J,Kondoh G.: "Conditional gene targeting and its application in the skin"J.Dermatol.Sci.. 23. 147-154 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawamoto S,Niwa H,Tashiro F,Sano S,Kondoh G,Takeda J,Tabayashi K,Miyazaki J.: "A novel reporter mouse strain that expresses enhanced green fluorescen protein upon Cre-mediated recombination."FEBS Lett.. 470. 263-268 (2000)

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

    • Related Report
      2000 Annual Research Report
  • [Publications] Sano S,Takeda J,Yoshikawa K,Itami S.: "Tissue regeneration : hair follicle as a model."J Invest Dermatol Symp Proc.. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 佐野栄紀: "毛包成長とSTAT3"臨床皮膚科. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sano S.: "Keratinocyte specific ablation of Stat3 exhibits impaired skin remold"EMBO J. 18. 4657-4668 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takeda J.: "Conditional gene targeting and its application in the skin"J. Dermatol. Sci. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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