Insulin-like growth factor binding protein-1 levels are increased in patients with IgA nephropathy

• Published in: Biochemical and biophysical research communications Vol. 399; no. 2; pp. 144 - 149
• Main Authors: Tokunaga, Koki, Uto, Hirofumi, Takami, Yoichiro, Mera, Kumiko, Nishida, Chika, Yoshimine, Yozo, Fukumoto, Mayumi, Oku, Manei, Sogabe, Atsushi, Nosaki, Tsuyoshi, Moriuchi, Akihiro, Oketani, Makoto, Ido, Akio, Tsubouchi, Hirohito
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-08-2010
• Subjects: 60 APPLIED LIFE SCIENCES; Adult; Animals; CELL PROLIFERATION; Female; FIBROSIS; FILTRATION; Gene Expression Profiling; Glomerulonephritis, IGA - blood; Glomerulonephritis, IGA - genetics; Glomerulonephritis, IGA - pathology; GROWTH FACTORS; Humans; IgA nephropathy; IGF-1; IGFBP-1; Immunoglobulin A - blood; IMMUNOGLOBULINS; INJURIES; INSULIN; Insulin-Like Growth Factor Binding Protein 1 - blood; Insulin-Like Growth Factor Binding Protein 1 - genetics; Kidney - metabolism; Kidney - pathology; KIDNEYS; Male; Mesangial cell proliferation; MICE; Mice, Inbred Strains; Middle Aged; Oligonucleotide Array Sequence Analysis; PATHOGENESIS; PATHOLOGY; PATIENTS; POLYMERASE CHAIN REACTION; Serum level; Young Adult; IGFBP-1; Serum level; IGF-1; IgA nephropathy; Mesangial cell proliferation
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2010.07.032

► IGFBP-1 mRNA over express in kidneys obtained from mice model of IgA nephropathy. ► Serum IGFBP-1 levels are high in patients with IgA nephropathy. ► Serum IGFBP-1 levels correlate with renal function and the severity of renal injury.
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.