1998 Fiscal Year Final Research Report Summary
Significance of mesangial cell aging in glomerulonephritis
| Project/Area Number |
09671177
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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 | Showa University |
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Principal Investigator |
YOSIMURA Ashio Showa University School of Medicine Associate professor, 医学部, 助教授 (50211660)
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| Project Period (FY) |
1997 – 1998
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| Keywords | senescence / telomere / telomerase / mesangial cell / oxygen radicals / glomerulonephritis / renal failure / hemodialysis therapy |
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| Research Abstract |
Aging is one of the most important factors in the decline of renal function in various kidney diseases. In most somatic cells, the telomere length is shortened each time the cell divides. When the telomere length reaches a critical point, the cell ceases to divide which leads to senescence. In human glomerular diseases numaerous division of mesangial cells may occur in the long clinical course, and therefore it is expected that the senescence of mesangial cells may be important in progression of glomerular diseases. Thus, telomere shortening reflects senescence and altered cellular function in mesangial cells. We studied to show the change of telomere length by aging in mesangial cells and furthermore to investigate the effect of oxygen radicals on telomere length, because oxygen radicals are one of the most powerful factors for inducing cell aging. Human mesangial cells (HMC) are isolated and cultured from a 45 year-old man. Genomic DNA from passages 4, 6 and 7 was digested respective
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ly, and Southern blot analysis for telomere DNA was performed using the telomere repeat generated by polymerase chain reaction as a probe. Shortening of telomere length was demonstrated from passages 4 to 7. Furthermore telomere shortening was accelerated in HMC after continuous exposure for hydrogen peroxide as a source of oxygen radicals. We also succeeded to induce telomerase activity in HMC with oxygen radicals exposure. We conclude that cultured HMC develop features of senescence over time, as documented by a significant shortening of the telomere. This process is accentuated by reactive oxygen species. Oxidant- and aging-induced senescence may play a role in aging associated glomerulosclerosis.
As a next study, we investigated telomere length of 5 patients with long-term hemodialysis and of age-matched 5 healthy persons respectively, because some manifestations of aging, such as atherosclerosis and skin roughness, were commonly observed in patients with end-stage renal diseases or hemodialysis therapy. Telomere length of hemodialysis patients (9.8±2.1 kbp) was significantly shorter than healthy persons (10.7±2.9, p<0.05). From these, prolonged course of chronic renal failure or long-term hemodialysis therapy would accelerate aging. Less
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