1. Protective effects of tubular liver-type fatty acid-binding protein against glomerular damage in murine IgA nephropathy.
- Author
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Zuo N, Suzuki Y, Sugaya T, Osaki K, Kanaguchi Y, Wang L, and Tomino Y
- Subjects
- Aldehydes metabolism, Animals, Blotting, Western, Cells, Cultured, Chemokine CCL2 genetics, Chemokine CCL2 metabolism, Fatty Acid-Binding Proteins genetics, Female, Glomerulonephritis, IGA metabolism, Glomerulonephritis, IGA pathology, Heme Oxygenase-1 genetics, Heme Oxygenase-1 metabolism, Humans, Inflammation metabolism, Inflammation pathology, Kidney Diseases etiology, Kidney Tubules, Proximal metabolism, Kidney Tubules, Proximal pathology, Mesoderm metabolism, Mesoderm pathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Oxidative Stress, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Tumor Necrosis Factor-alpha immunology, Tumor Necrosis Factor-alpha metabolism, Fatty Acid-Binding Proteins metabolism, Glomerulonephritis, IGA complications, Kidney Diseases prevention & control, Kidney Glomerulus pathology
- Abstract
Background: Liver-type fatty acid-binding protein (L-FABP) in proximal tubules was reported to have renoprotective roles in experimental tubulointerstitial diseases via its anti-oxidative properties. Since tubuloglomerular cross-talk was recently discussed in the progression of renal diseases, to investigate whether tubular L-FABP may have an impact on the progression of glomerular damage, we induced IgA nephropathy (IgAN) in mice (Tg) transgenically tubular overexpressing human L-FABP (hL-FABP)., Methods: We reconstituted IgAN by bone marrow transplantation (BMT) from IgAN-prone mice into Tg and wild-type (WT) mice. Renal damage was evaluated at 6 and 12 weeks after BMT. During in vitro experiments, mesangial cells (MC) were stimulated by aggragated IgA (AIgA), and their supernatants (AIgA-MC medium) were collected. Stable cell line of mouse proximal tubular cell (mProx) transfected with or without hL-FABP gene was cultured with the AIgA-MC medium., Results: Although mesangial IgA deposition and serum IgA level were not different between WT (WT/ddY) and Tg (Tg/ddY) recipients, WT/ddY mice showed a significantly higher urinary albumin level and mesangial matrix expansion with a significantly higher glomerular damage score. Furthermore, CD68 + macrophage infiltration was also significantly attenuated in Tg/ddY mice. Up-regulation of renal hL-FABP was associated with significant suppression of renal heme oxygenase-1 (HO-1) expression and accumulation of 4-hydroxy-2-nonenal (4-HNE) and MCP-1 expression in Tg/ddY mice. In vitro experiments showed that AIgA-MC medium and recombinant TNF-α significantly up-regulated hL-FABP expression, which was partially blocked by anti-TNF-α antibody, and major mediators of oxidative stress (HO-1 and 4-HNE) and inflammation (MCP-1). Importantly, such up-regulation of the mediators in mProx with hL-FABP was significantly suppressed much more than that in mProx., Conclusions: Tubular L-FABP activated by MC-origin humoral factors may lessen progression of glomerular damage at early stages of IgAN by reducing oxidative stress and inflammatory mediators.
- Published
- 2011
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