2005 Fiscal Year Final Research Report Summary
Pathophysiological significance of urotensin/urocortin family
| Project/Area Number |
16590919
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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 |
Endocrinology
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| Research Institution | Kyoto Medical Center |
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Principal Investigator |
NARUSE Mitsuhide Kyoto Medical Center, Clinical Research Institute of Endocrine and Metabolic Disease, Director, 臨床研究センター・内分泌研究部, 部長 (40120018)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATA Daisuke Kyoto Medical Center, Clinical Research Institute of Endocrine and Metabolic Disease, Division Chief, 臨床研究センター・内分泌研究部, 室長 (40393194)
IMAKI Toshihiro Nippon Medical Collage, Institute of Gerontology, Associate Professor, 医学部・老人病研究所, 助教授 (50183190)
TANABE Akiyo Tokyo Women's Medical University, Department of Medicine, Clinical associate, 医学部・第2内科, 助手 (00236655)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Urotensin / Urocortin / Cardiac remodeling / Collagen / Brain natriuretic peptide / Endothelin / Osteopontin |
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| Research Abstract |
Urotensin II (UT II) and urocortin (UC) are biologically active peptides of the urotensin/urocortin family and suggested to be involved in the regulation of cardiovascular homeostasis. Pathophysiological significance of the peptides however remains to be elucidated. In the present study, effects of UT II and UC on the cardiovascular system were investigated in vivo in normotensive and hypertensive rats (SHR-SP) and in vitro using cultured vascular smooth muscle cells (hCASMC) and endothelial cells (HUVEC). Blood pressure and expression of various markers for fibrosis, inflammation, and cell growth were determined at the levels of protein synthesis and mRNA expression. Both of UT II and UC significantly increased collagen, BNP, ET-1,and osteopontin at the non-pressor as well as pressor dose in vivo. Sensitivity to UT II and UC was accelerated in hypertensive rats compared to normotensive rats. In addition, these peptides significantly increased MAPK (ERK, JNK) activity and mRNA levels of the inflammatory cytokines in the hCASMC and HUVEC in a dose-dependent and time-dependent manner. These results suggest that both of UT II and UC are biologically active peptides deeply involved in the modulation of cardiovascular remodeling.
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