2007 Fiscal Year Final Research Report Summary
Gene expression profiling of peripheral blood mononuclear cells from patients with minimal change nephrotic syndrome
| Project/Area Number |
17590817
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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 | Akita University |
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Principal Investigator |
KOMATSUDA Atsushi Akita University, School of Medicine, Lecturer (70272044)
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| Co-Investigator(Kenkyū-buntansha) |
WAKUI Hideki Akita University, School of Medicine, Associate Professor (70240463)
ITOH Hideaki Akita University, Faculty of Engineering and Resource Science, Professor (80168369)
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| Project Period (FY) |
2005 – 2007
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| Keywords | MCNS / SAGE / cDNA microarray / chemokine ligand 13 / HSPC159 / MPO-ANCA-associated glomeruloneohritis / SLE / TRAIL |
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| Research Abstract |
It is hypothesized that minimal change nephrotic syndrome (MCNS) is a consequence of immune cell dysfunction that may lead to release of glomerular permeability factors. However, the nature of such factors remains uncertain. To identify of peripheral blood mononuclear cells (PBMC) genes that are potentially involved MCNS, various novel methods, such as a subtracted cDNA library screening, a serial analysis of gene expression (SAGE) and a cDNA microarray-based method, have been used. By SAGE, we found that the expression of TRAIL is higher in relapse than that in CR in patients with MCNS. We also perform a cDNA microarray-analysis, and found that CCL13 and HSPC159 mRNA expressions in PBMC are up-regulated specifically in MCNS patients during the nephrosis phase. Further studies are necessary to clarify whether theses expression changes are directly involved in the pathophysiologic processes of MCNS.
In the up-regulated genes in the nephrosis PBMC sample, there is a proinflammatory protein, S100A12, which is secreted by activated neutrophils. We investigated serum levels of S100A12 in patients with small-vessel vasculitis, myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated pauci-immune glomerulonephritis. We found that increased serum S100A12 levels correlate with clinical, laboratory, and pathological parameters of disease activity in patients with MPO-ANCA-associated glomerulonephritis. Serum S100A12 level may be one of useful markers of disease activity in MPO-ANCA-associated glomerulonephritis.
Recently, TRAIL is involved in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we examined whether expression levels of TRAIL depend on SLE activity. We found that TRAIL mRNA expression levels in PBMC closely correlate with the SLE disease activity index and circulating immune complex levels. These results indicate an important role for TRAIL in the pathogenesis of SLE.
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