2002 Fiscal Year Final Research Report Summary
Relation of adrenomedullin and apoptosis in renal diseases
| Project/Area Number |
10218209
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Dokkyo University School of Medicine |
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Principal Investigator |
ISHIMITSU Toshihiko Dokkyo Univ. Sch. Med., HT & Cardiorenal Med., Assoc. Prof., 医学部, 助教授 (80232346)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Naohiko Dokkyo Univ. Sch. Med., HT & Cardiorenal Med., Lecturer, 医学部, 講師 (90254945)
MATSUOKA Hiroaki Dokkyo Univ. Sch. Med., HT & Cardiorenal Med., Professor, 医学部, 教授 (20111544)
ONO Hidehiko Dokkyo Univ. Sch. Med., HT & Cardiorenal Med., Lecturer, 医学部, 講師 (70214187)
NISHIKIMI Toshio Dokkyo Univ. Sch. Med., HT & Cardiorenal Med., Assoc. Prof., 医学部, 助教授 (80291946)
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| Project Period (FY) |
1998 – 2002
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| Keywords | adrenomedullin / renal disease / hypertension / apoptosis / gene polymorphism / remodeling / fibrosis |
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| Research Abstract |
Sequencing of genomic DNA encoding human adrenomedullin (AM) gene and the adjacent region revealed that the gene is flanked by informative microsatellite marker of CA repeats. In Japanese, there existed four allele types with CA repeat numbers of 11,13,14 and 19. The frequency of 19-repeat allele was increased in patients with essential hypertension or type 2 diabetic nephropathy as compared with healthy subjects : It is suggested. that the 19-repeat allele is associated with the genetic risks for developing hypertension and diabetic nephropathy. In addition, there were two single nucleotide polymorphisms (SNP) in intron 1 (+223A/C) and intron 3 (+1100C/G) which were linked each other. Healthy subjects carrying +223C allele tended to have high serum triglycerides, and the allele may be related to the alteration in lipid metabolism.
In severely hypertensive SHR given L-NAME showed apoptosis of myocardial interstitial cells and glomerular and tubular epithelial cells. It is suggested that remodeling of cardiovascular tissues is modified by the balance of cell proliferation and apoptosis. AM was positively stained by immunohistochemistry in perivascular fibroblasts, sclerotic glomeruli and atrophied tubular epithium. In these tissues, mRNA expressions of AM, caspase-3 and TGF-β were increased. It is suggested that AM plays an compensatory role against apoptotic and fibrotic changes in cardiovascular tissues. Chronic infusion of AM alleviated renal injuries in rats with salt-induced hypertension. In human renal biopsy tissues, AM mRNA expression was increased in malignant nephrosclerosis and caspase-3 mRNA expression was increased in IgA nephropathy with poor prognosis. Thus, renal injury is supposed to be promoted by apoptosis in glomerulonephritis and AM may counteract against the progression of nephrosclerosis.
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