2005 Fiscal Year Final Research Report Summary
Functional analysis of mesangial cell syncytium and elucidation of mechanisms involving progressive glomerulosclerosis
| Project/Area Number |
15390266
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Niigata University |
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Principal Investigator |
OITE Takashi Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (60018744)
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| Co-Investigator(Kenkyū-buntansha) |
MORIOKA Tetsuo Niigata University, Institute of Medicine and Dentistry, Associate Professor, 医歯学系, 助教授 (00210146)
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| Project Period (FY) |
2003 – 2005
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| Keywords | renal glomeruli / mesangial cells / syncytium / gap junction / glomerulosclerosis / experimental animals / hemodynamic analysis / disturbance of functional regulation |
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| Research Abstract |
1.We have clarified that connexin 43 play an important role of intercellular communication among mesangial cells in co-culture system with endothelial cells, isolated glomeruli, and in vivo. In addition, we found out that co-ordination of renin secretion from granular cells in the paraglomerular apparatus was induced by signal transduction via ATP-purinergic receptor.
2.We drew a running hypothesis from our experimental results that loss of physiopathological interaction between endothelial and mesangial cells may cause disturbance of mesagial cell syncytial function, leading to irreversible progression of glomerulosclerosis.
3.In high concentration of glucose, the availability of endothelial NOS in cultured glomerular endothelial cells was decreased dramatically, perhaps, by overproduction of superoxide.
4.We established a permanent line of cultured human glomerular endothelial cells by transformation with SV40 virus. This cell line is very useful for the standardization of anti-endothelial cell antibody and for establishing culture system of glomerular endothelial cells at large scale.
5.We determined the functional epitope of rat Thy-1.1 molecule recognized by monoclonal antibody, named by 1-22-3, one kind of anti-Thy-1.1 antibodies, by the GST-fusion protein method. In vivo binding of 1-22-3 expressed on the surface of mesangial cells results in severe glomerulonephritis.
6.Comparing one-kidney and two-kidney groups induced by 1-22-3 injection, we could determine the turning period when the renal disease will divide into reversible or irreversible course.
7.Using EGFP-transgenic rats, we could determine the involvement of bone marrow-derived endothelial precursor cells in the regeneration of glomerular endothelial cells. In conclusion, bone marrow-derived endothelial precursor cells recruited play an important role in repairing glomerular injury after severe mesangial cell damage.
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