2004 Fiscal Year Final Research Report Summary
Skin regeneration : hair follicle as a model for signal trunsduction
| Project/Area Number |
14370259
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
ITAMI Satoshi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (30136791)
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| Co-Investigator(Kenkyū-buntansha) |
INUI Shigeki Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30324750)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Tissue regeneration / Hair follicle / Androgen / TGF-β1 / Stat3 / HGF / Wound healing / Bone marrow stem cell |
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| Research Abstract |
One of the typical example of the signal transduction in the human hair cycle progression is androgen-androgen receptor system. In order to know the mode of androgen action in human hair follicles, we developed an in vitro coculture system using DPC and follicular epithelial cells. Androgen significantly stimulated the proliferation of follicular epithelial cells cocultured with beard or axillary DPC, suggesting that these DPC produce androgen-dependent diffusible growth factors. On the other hand, we could identify inhibitory roles of androgen on the growth follicular epithelial cells cocultured with DPC derived from the human bald frontal scalps, when DPC were transfected with the AR expression vector. Androgen-inducible TGF-β1 derived from DPCs plays a central role for the growth suppression.
Stat3 plays a crucial role in transducing a signal for the anagen initiation and wound healing. The anagen initiation represents vertical wound healing. Hepatocyte growth factor (HGF) strongly a
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ctivates stat3 in the keratinocytes and promoted migration of keratinocytes. Neutralizing anti-HGF IgG delayed skin wound healing in normal mice. Moreover, exogeneous HGF stimulated cutaneous wound healing in diabetic mice model. HGF would be a potential therapeutic approach for the treatment of chronic skin ulcer.
Diabetic foot ulcers with exposed bones commonly result in amputation. Our study that early aggressive debridement of diabetic foot ulcers with exposed bones down to a bleeding vascularized base and then grafting epidermal sheets significantly improves healing and reduces the rate of amputation. The usefulness of bone marrow cells in accelerating wound healing has not been evaluated despite increasing evidence that bone marrow contains mesenchymal stem cells that have multipotentiality to differentiate into various types of cells after they enter the microenvironment of a specific tissue (niche). We founfd that bone marrow cells accelerate the healing of wounds at least in part through their differentiation into wound myofibroblasts. Thus, treatment of wounds with bone marrow cells and a supportive occlusive dressing is effective in promoting the formation of healthy granulation tissue and also for the preparation of an ideal wound bed. Less
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[Book] Androgen and androgen receptor - Mechanisms, functions, and clinical applications. (Chang C (ed))2002
Author(s)
Itami S, Inui S, Uno H, Pan Huei-Ju, Chang E, Takayasu S, Ye F, Imamura K, Seki T, Ideta R, Aoki H, Adachi K, Price V, Kurata S, Collins L, Heinlein CA, Chang C
Total Pages
411-476
Publisher
Kluwer Academic Publishers, Norwell, Massachusetts, USA
Description
「研究成果報告書概要(欧文)」より
