Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy.
The mechanisms underlying the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) are not well understood. In this study, we examined gene expression profiles in kidneys obtained from mice with high serum IgA levels (HIGA mice), which exhibit features of human IgAN. Female inbred HIGA, established from the ddY line, were used in these experiments. Serum IgA levels, renal IgA deposition, mesangial proliferation, and glomerulosclerosis were increased in 32-week-old HIGA mice in comparison to ddY animals. By microarray analysis, five genes were observed to be increased by more than 2.5-fold in 32-week-old HIGA in comparison to 16-week-old HIGA; these same five genes were decreased more than 2.5-fold in 32-week-old ddY in comparison to 16-week-old ddY mice. Of these five genes, insulin-like growth factor (IGF) binding protein (IGFBP)-1 exhibited differential expression between these mouse lines, as confirmed by quantitative RT-PCR. In addition, serum IGFBP-1 levels were significantly higher in patients with IgAN than in healthy controls. In patients with IgAN, these levels correlated with measures of renal function, such as estimated glomerular filtration rate (eGFR), but not with sex, age, serum IgA, C3 levels, or IGF-1 levels. Pathologically, serum IGFBP-1 levels were significantly associated with the severity of renal injury, as assessed by mesangial cell proliferation and interstitial fibrosis. These results suggest that increased IGFBP-1 levels are associated with the severity of renal pathology in patients with IgAN.
Tokunaga
Koki
K
Department of Digestive and Life-Style Related Disease, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Uto
Hirofumi
H
Takami
Yoichiro
Y
Mera
Kumiko
K
Nishida
Chika
C
Yoshimine
Yozo
Y
Fukumoto
Mayumi
M
Oku
Manei
M
Sogabe
Atsushi
A
Nosaki
Tsuyoshi
T
Moriuchi
Akihiro
A
Oketani
Makoto
M
Ido
Akio
A
Tsubouchi
Hirohito
H
D000328:Adult; D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000235:genetics*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult
D007070:Immunoglobulin A; D018970:Insulin-Like Growth Factor Binding Protein 1