2002 Fiscal Year Final Research Report Summary
Mitochondrial DNA mutations in focal segmental glomerular sclerotic lesions
| Project/Area Number |
13671097
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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 |
Kidney internal medicine
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| Research Institution | UNIVERSITY OF TSUKUBA |
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Principal Investigator |
YAMAGATA Kunihiro University of Tsukuba, Institute of Clinical Medicine, Associate Professor of Medicine, 臨床医学系, 助教授 (90312850)
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| Co-Investigator(Kenkyū-buntansha) |
KOYAMA Akio University of Tsukuba, Institute of Clinical Medicine, Professor of Medicine, 臨床医学系, 教授 (80111384)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Focal and segmental glomerular sclerosis (FGS) / glomerular epithelial cells / Glomerulonephritis / Mitochondrial DNA / glomerular sclerosis / IgA nephropathy / Heteroplasmy / 膜性腎症 |
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| Research Abstract |
Glomerular epithelial cells (GEpC) are primary pathogenic sites in focal segmental glomerular sclerosis (FGS) lesions. GEpCs are regarded as terminally differentiated cells and do not proliferate. This characteristic is the same for neuron cells and muscular cells, which are major sites of mtDNA mutations accumulation. We screened for mitochondrial DNA (mtDNA) mutations in renal biopsy specimens from primary FGS patients and also from IgA nephropathy patients as a secondary FGS subject and as a control. MtDNA extracted from kidney biopsy specimens was amplified with appropriate primer pairs for studying mtDNA point mutations 3243 A to G, 3271 T to C, 8344 A to G, 8993 T to G, C and the common deletion (a 4977-bp deletion spanning mtDNA nucleotide pairs 8469 to 13447). In situ amplification of both total mtDNA and the common deletion were also performed. Two patients with FGS had a 3243 A to G point mutation and 12 patients with FGS, and 7 patients with IgA nephropathy accompanied by glomerular sclerotic lesions, had the common deletion in their kidney tissue. No patient showed mtDNA mutations 3271 T to C, 8344 A to G or 8993 T to G or C. The degree of heteroplasmy for 3243 A to G point mutation was more than 85%, however, the heteroplasmy for the common deletion was less than 1%. Using in situ PCR, normal mtDNA was mainly distributed to the tubular epithelium, and mtDNA with the common deletion was mainly distributed among GEpC. In conclusion, it is suggested that mtDNA mutations are distributed to the GEpC in some patients with primary FGS and secondary FGS with IgA nephropathy. These mutations may be related to GEpC damage.
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[Publications] Yamagata K, Muro K, Usui J, Hagiwara M, Kai H, Arakawa Y, Shimizu Y, Tomida C, Hirayama K, Kobayashi M, Koyama A: "Mitochondrial DNA mutations in focal segmental glomerulosclerosis lesions"J Am Soc Nephrol. 13・7. 1816-1823 (2002)
Description
「研究成果報告書概要(和文)」より
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[Publications] Yamagata K, Muro K, Usui J, Hagiwara M, Kai H, Arakawa Y, Shimizu Y, Tomida C, Hirayama K, Kobayashi M, Koyama A: "Mitochondrial DNA mutations in focal segmental glomerulosclerosis lesions"J Am Soc Nephrol. 13・7. 1816-1823 (2002)
Description
「研究成果報告書概要(欧文)」より
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