Analysis of the role of keratinocyte Stat3 using the epithelia-specific gene ablation technology.
| Project/Area Number |
11670828
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Osaka University |
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Principal Investigator |
SANO Shigetoshi Graduate School of Medicine, Osaka University Lecturer, 医学系研究科, 講師 (80273621)
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| 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)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| 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)
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| Keywords | epidermal keratinocyte / Stat3 / Signal transduction / growth factor / migration / wound healing / hair cycle / ulcer formation |
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| 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.
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Report
(3 results)
Research Products
(8 results)
