Adrenomedullin gene transcription is decreased in peripheral blood mononuclear cells of patients with IgA nephropathy.
We measured mRNA levels of adrenomedullin (AM), C-type natriuretic peptide (CNP), vascular endothelial growth factor (VEGF), interleukin 1beta (IL-1beta) and interleukin 6 (IL-6) in peripheral blood mononuclear cells (PBMC) of patients with IgA nephropathy. To evaluate these mRNA levels, we employed a real-time quantitative PCR method which was performed using a hybridization probe labeled with two fluorescence dyes. This strategy was found to afford the standard curves with a high correlation, suggesting that this method is useful for evaluations of mRNA levels. By this method, levels of AM, CNP, VEGF, IL-1beta and IL-6 mRNA in PBMC of 49 IgA nephropathy patients and 35 healthy volunteers were evaluated. Among the mRNAs examined, AM mRNA levels were significantly lower in severe-grade than in mild-grade IgA nephropathy patients. Furthermore, AM mRNA levels correlated with CNP mRNA levels in PBMC of patients with IgA nephropathy, and each peptide generated from these mRNAs has antiproliferative effects on mesangial cells. These data indicate that gene expression of AM in PBMC is regulated according to the pathophysiological states of IgA nephropathy and that decreased AM production may contribute to the progression of IgA nephropathy.
Kubo
A
A
1st Department of Internal Medicine, Nara Medical University, Kashihara, Japan.
Nishitani
Y
Y
Minamino
N
N
Kikumoto
K
K
Kurioka
H
H
Nishino
T
T
Iwano
M
M
Shiiki
H
H
Kangawa
K
K
Dohi
K
K
D053607:Adrenomedullin; D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics; D005786:Gene Expression Regulation; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics; D008875:Middle Aged; D020098:Natriuretic Peptide, C-Type / Q000235:genetics; D010455:Peptides / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017931:DNA Primers; D016228:Endothelial Growth Factors; D007375:Interleukin-1; D015850:Interleukin-6; D008222:Lymphokines; D010455:Peptides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020098:Natriuretic Peptide, C-Type; D053607:Adrenomedullin