2004 Fiscal Year Final Research Report Summary
Involvement of mitochondrial function and mitochondrial DNA mutations in focal segmental glomerulosclresosis
| Project/Area Number |
15590841
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
YAMAGATA Kunihiro University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associate Professor of Medicine, 大学院・人間総合科学研究科, 助教授 (90312850)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOYAMA Akio University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor of Medicine, 大学院・人間総合科学研究科, 教授 (80111384)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Focal and segmental glomerular sclerosis / mitochondria / Mitochondrial DNA / mitochondrial protein / oxidative stress / podocyte / deletion mutation |
|---|
| Research Abstract |
In order to clarify the involvement of mitochondrial DNA(mtDNA) in the pathogenesis of focal segmental sclerosis lesions, we analyzed mtDNA status by several molecular and histochemical approaches in relation to pathological changes occurring with age in the kidney of the Fawn Hooded hypertensive rat. Blood pressure and proteinuria were gradually elevated with aging in all rats. Also the 4834 deletion of mtDNA in kidney tissue gradually increased in the kidneys as observed. The main localization of the mtDNA 4834 deletion mutation was seen to be in podocytes and these changes became obvious after 20 weeks. MtDNA in podocytes was shown to react with an anti 8-OHdG antibody, and this change was almost constant from 8 weeks on. Further, the segmental absence of COX I in glomeruli was observed after 20 weeks, Intra-glomerular COX I expression was significantly reduced, however, COX IV expression was not changed. In conclusion, it is suggested that the mtDNA of podocytes suffers critical reactive oxygen damage. Furthermore, in situ mtDNA damage, and mtDNA-encoded mitochondrial enzyme deficiency were also observed. These results suggest that glomerular epithelial mitochondrial dysfunction might be an important pathogenic change in focal segmental sclerosis lesions.
|
-
-
-
-
-
-
-
[Journal Article] Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.2004
Author(s)
Koyama A, Sharmin S, Sakurai H, Shimizu Y, Hirayama K, Usui J, Nagata M, Yoh K, Yamagata K, Muro K, Kobayashi M, Ohtani K, Shimizu T, Shimizu T.
-
Journal Title
Kidney Int. 66(1)
Pages: 121-132
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Journal Article] Treatment with the purine synthesis inhibitor mizoribine for ANCA-associated renal vasculitis.2004
Author(s)
Hirayama K, Kobayashi M, Hashimoto Y, Usui J, Shimizu Y, Hirayama A, Yoh K, Yamagata K, Nagase S, Nagata M, Koyama A.
-
Journal Title
Am J Kidney Dis. 44(1)
Pages: 57-63
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Glomerular crescents predominantly express cadherin-catenin complex in pauci-immune-type crescentic glomerulonephritis.2003
Author(s)
Usui J, Kanemoto K, Tomari S, Shu Y, Yoh K, Mase K, Hirayama A, Hirayama K, Yamagata K, Nagase S, Kobayashi M, Nitta K, Horita S, Koyama A, Nagata M.
-
Journal Title
Histopathology 43
Pages: 173-179
Description
「研究成果報告書概要(欧文)」より
