Up-regulation of TRAIL mRNA expression in peripheral blood mononuclear cells from patients with minimal-change nephrotic syndrome

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2005-03, Vol.20 (3), p.539-544
• Main Authors: Okuyama, Shin, Komatsuda, Atsushi, Wakui, Hideki, Aiba, Namiko, Fujishima, Naohito, Iwamoto, Keiko, Ohtani, Hiroshi, Sawada, Ken-ichi
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Apoptosis Regulatory Proteins; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Case-Control Studies; Emergency and intensive care: renal failure. Dialysis management; Female; gene expression profile; Gene Expression Profiling; Glomerulonephritis; Humans; Intensive care medicine; Leukocytes, Mononuclear - metabolism; Male; Medical sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Middle Aged; minimal-change nephrotic syndrome; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nephrosis, Lipoid - genetics; Nephrosis, Lipoid - metabolism; Remission, Spontaneous; RNA, Messenger - metabolism; serial analysis of gene expression; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; TNF-Related Apoptosis-Inducing Ligand; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; tumour necrosis factor-related apoptosis-inducing ligand; Up-Regulation - genetics
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfh673

Background. Minimal-change nephrotic syndrome (MCNS) is considered to be associated with T-cell dysfunction and with the abnormal secretion of putative glomerular permeability factors; however, the nature of such factors remains elusive. Methods. To identify up-regulated genes during the nephrosis phase, we undertook serial analyses of gene expression (SAGE) in peripheral blood mononuclear cells (PBMC) from a patient with MCNS sampled during the nephrosis and remission phases. To confirm the SAGE results, we performed quantitative real-time reverse transcription–polymerase chain reaction (RT–PCR) analyses. We also measured the serum levels of the identified gene product in nephrosis and remission samples from 29 MCNS patients, 57 patients with nephrotic syndrome due to other types of glomerular diseases and 30 healthy individuals. Results. Using more than 20 000 SAGE tags, we identified 15 functionally known genes that were up-regulated (≥4-fold) in PBMC from the MCNS patient during the nephrosis phase. For further examination, we selected two genes encoding secretory proteins, namely tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and tissue inhibitor of metalloprotease 1. Real-time RT–PCR analysis confirmed a higher expression of TRAIL mRNA in PBMC during nephrosis than during remission in eight MCNS patients. The expression pattern of TRAIL mRNA, however, was variable among four patients with membranous nephropathy. There was no significant increase of serum levels of a soluble form of TRAIL in MCNS patients during the nephrosis phase. Conclusions. These results suggest that the intracellular TRAIL mRNA expression in PBMC is up-regulated in MCNS patients during the nephrosis phase. This change may represent either an epiphenomenon or it may provide a potential explanation for the altered T-cell function in MCNS.