2005 Fiscal Year Final Research Report Summary
Regulatory mechanism of mast cell function by the TGF-β family
| Project/Area Number |
15580268
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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 |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Azabu University |
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Principal Investigator |
FUNABA Masayuki Azabu University, School of Veterinary Medicine, Assistant Professor, 獣医学部, 講師 (40238655)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Teruo Azabu University, School of Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (60151297)
MURAKAMI Masaru Azabu University, School of Veterinary Medicine, Professor, 獣医学部, 教授 (80271360)
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| Project Period (FY) |
2003 – 2005
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| Keywords | TGF-β family / mast cell / signal transduction / cell differentiation |
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| Research Abstract |
The multivalent binding of an antigen to receptor bound IgE and the subsequent aggregation of the high affinity receptor for IgE (FcεRI) provide the trigger for activation of mast cells, leading to synthesis and secretion of various inflammatory molecules including histamine. The previous study indicated gene induction of activin A, a member of the TGF-β family, in mast cells in response to the activation (Cell Signal., 15:605.2003). The present study examined to clarify the regulatory mechanism of mast cell function by the TGF-β family. Mast cells migrated toward TGF-β1 and activin A. These ligands also had activities to inhibit cell proliferation and to stimulate maturation of mast cells. Furthermore, the ligands induced genes related to the maturation (J.Leukoc.Biol., 73:793.2003; Cell.Signal., 17:121.2005, 18:256.2006). To explore the modulation of mast cell function by the TGF-β family at the molecular level, genes induced during the initial phase of treatment with TGF-β1 and activin A were examined in mast cells. As the result, tocopherol-associated protein (Tap) was identified as a TGF-β/activin-inducible gene, which was restricted in mast cells and enhanced TGF-β/activin signaling (in preparation). MITF, a tissue-specific transcription factor, is involved in mast cell maturation. Thus, relationship between MITF and the TGF-β family pathway was further examined. The results suggested that 1)MITF associated with Smad2/3, signal mediators for the TGF-β/activin pathway, 2)MITF negatively regulated Smad2/3 signaling, and 3)expression of Smad2/3 is decreased by the expression of MITF.
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