| Project/Area Number |
14572173
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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 |
応用薬理学・医療系薬学
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| Research Institution | NATIONAL RESEARCH INSTITUTE FOR CHIOLD HEALTH AND DEVELOPMENT |
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Principal Investigator |
TANOUE Akito NATIONAL RESEARCH INSTITUTE FOR CHILD HEALTH AND DEVELOPMENT, DEPARTMENT OF PHARMACOLOGY, DIRECTOR, 薬剤治療研究部, 部長 (60301800)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJIMOTO Gozoh KYOTO UNIVERSITY GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, PROFESSOR, 大学院・薬学研究科・ゲノム創薬科学分野, 教授 (80172013)
HIRASAWA Akira NATIONAL RESEARCH INSTITUTE FOR CHIOLD HEALTH AND DEVELOPMENT, ASSOCIATE DIRECTOR, 実験薬理研究室, 室長 (70242633)
KOSHIMIZU Taka-aki NATIONAL RESEARCH INSTITUTE FOR CHIOLD HEALTH AND DEVELOPMENT, RESEARCHER, 共同研究員
OSHIKAWA Sayuri NATIONAL RESEARCH INSTITUTE FOR CHIOLD HEALTH AND DEVELOPMENT, RESEARCHER, 共同研究員
KITAGAWA Yoko NATIONAL RESEARCH INSTITUTE FOR CHIOLD HEALTH AND DEVELOPMENT, RESEARCHER, 共同研究員
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | animal models / drugs / receptors / DNA chip / micrarray |
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| Research Abstract |
Sphingosine 1-phosphate(S1P) is known to regulate cell proliferation, apoptosis, and motility. Recently, we have reported that S1P and its analogue dihydro-S1P(DHS1P) promote proliferation of rat cultured mesangial cells. To investigate the signaling mechanisms underlying S1P- and DHS1P-induced mesangial cell proliferation, we performed cDNA microarray analysis of gene expression during mesangial cell proliferation. In terms of the overall pattern, gene expression waves induced by S1P and DHS1P were similar to those induced by a potent mesangial mitogen platelet-derived growth factor(PDGF), whereas we found several genes, such as two growth factors, connective tissue growth factor(CTGF) and heparin-binding EGF-like growth factor(HB-EGF), which were induced by the sphingolipids, but not by PDGF. Cluster analysis also identified calcium-dependent molecules highly expressed in DHS1P-stimulated cells compared to S1P-stimulated cells. Calcium mobilization analysis showed that DHS1P had higher magnitudes of intracellular calcium mobilization than S1P, suggesting that SIP and DHS1P differentially regulate intracellular calcium mobilization, possibly leading to different gene expression in mesangial cells. The large-scale monitoring of gene expression performed here allows us to identify S1P-induced transcriptional properties during mesangial cell proliferation.
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