| Project/Area Number |
14370080
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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 |
Experimental pathology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
SAWADA Norimasa Sapporo Medical University, School of Medicine, Professor, 医学部, 教授 (30154149)
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Takashi Sapporo Medical University, School of Medicine, Assistant Professor, 医学部, 助教授 (30260764)
CHIBA Hideki Sapporo Medical University, School of Medicine, Instructor, 医学部, 講師 (00295346)
TOBIOKA Hirotoshi Sapporo Medical University, School of Medicine, Instructor, 医学部, 講師 (90291559)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2002: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | tight junction / enodothelial cells / hepatocyte / nuclear receptor / gap junction / occludin / claudin / MAPK / PI3K |
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| Research Abstract |
Tight junctions are intercellular junctions adjacent to the apical most lateral membrane surface. They have two functions, a barrier function and a fence function. The former regulates the passage of ions, water and macromolecules through paracellular spaces and the latter maintains cell polarity. Once tight junctions are disturbed, illnesses such as edema, jaundice, diarrhea etc. can develop. In cancer cells, tight junctions decrease as dedifferentiation progresses. In this project, we demonstrated as follows.
1. Hepatocyte nuclear factor-4a is a key transcriptional factor of tight junction formation.
2. Claudin-1 and claudin-5 have consensus sequence in their cytoplasmic domains for MAP kinase and Protein kinase A, respectively.
3. Gap junctional interecellular communication enhances tight junction function.
4. In livers under pathological conditions, functions of gap and tight junctions are mainly regulated by p38 MAP kinase signal transduction pathway.
5. Occludin may in part mediate survival signal.
6. The expression of occludin progressively decreases in parallel with increasing grade of in human endometrial carcinomas.
7. Glyceraldehyde-derived advanced glycation end-products induces VEGF expression and reduces GDNF expression in human astrocytes, suggesting the main cause of diabetic retinopathy, in terms of highly permeable capillaries in the retina.
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