Urinary fatty acid binding protein in renal disease.
ABSTRACT The number of patients with end stage renal failure has been increasing throughout the world. The importance of measuring clinical parameters in renal injury has been emphasized for administering appropriate treatment and preventing a worsening of the disease. However, there are no clinically useful markers in predicting and monitoring the progression of renal disease. Liver type fatty acid binding protein (L-FABP) of 14.4 kDa is expressed in human proximal tubules. In order to evaluate the clinical significance of urinary L-FABP as a biomarker in renal disease, a monoclonal antibody against human L-FABP was developed and a two step sandwich enzyme linked immunosorbent assay (ELISA) method was established for determining human L-FABP in urine. In some clinical studies, urinary excretion of L-FABP was shown to be an excellent clinical marker that can help predict and monitor the progression of renal disease. The dynamics of renal L-FABP in pathophysiological settings has been revealed in experimental studies using transgenic mice with the human L-FABP gene. This review presents recent findings on the function and pathophysiological role of L-FABP, and summarizes the clinical importance of measuring urinary L-FABP in renal disease.
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ABSTRACT: Lipids are vital components of many biological processes and crucial in the pathogenesis of numerous common diseases, but the specific mechanisms coupling intracellular lipids to biological targets and signalling pathways are not well understood. This is particularly the case for cells burdened with high lipid storage, trafficking and signalling capacity such as adipocytes and macrophages. Here, we discuss the central role of lipid chaperones--the fatty acid-binding proteins (FABPs)--in lipid-mediated biological processes and systemic metabolic homeostasis through the regulation of diverse lipid signals, and highlight their therapeutic significance. Pharmacological agents that modify FABP function may provide tissue-specific or cell-type-specific control of lipid signalling pathways, inflammatory responses and metabolic regulation, potentially providing a new class of drugs for diseases such as obesity, diabetes and atherosclerosis.dressNature Reviews Drug Discovery 07/2008; 7(6):489-503. · 29.01 Impact Factor
Article: Protective effects of L-type fatty acid-binding protein (L-FABP) in proximal tubular cells against glomerular injury in anti-GBM antibody-mediated glomerulonephritis.[show abstract] [hide abstract]
ABSTRACT: In glomerulonephritis (GN), an overload of free fatty acids (FFA) bound to albumin in urinary protein may induce oxidative stress in the proximal tubules. Human liver-type fatty acid-binding protein (hL-FABP) expressed in human proximal tubules, but not rodents, participates in intracellular FFA metabolism and exerts anti-oxidative effects on the progression of tubulointerstitial damage. We examined whether tubular enhancement of this anti-oxidative action modulates the progression of glomerular damage in immune-mediated GN in hL-FABP chromosomal gene transgenic (Tg) mice. Anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) was induced in Tg and wild-type mice (WT). Proteinuria, histopathology, polymorphonuclear (PMN) influx, expression of tubulointerstitial markers for oxidative stress 4-hydroxy-2-Nonenal (HNE) and fibrosis (α-smooth muscle actin), proximal tubular damage (Kim-1), Peroxisome Proliferator-Activated Receptor γ (PPAR γ) and inflammatory cytokines [Monocyte Chemotactic Protein-1, tumor necrosis factor-alpha (TNF-α) and Transforming growth factor beta (TGF-β)] were analyzed. The mice were also treated with an angiotensin type II receptor blocker (ARB). The urinary protein level in Tg mice decreased significantly during the acute phase (~Day 5). Tg mice survived for a significantly longer time than WT mice, with an attenuation of tubulointerstitial damage score and expression of each tubulointerstitial damage marker observed at Day 7. Expression of inflammatory cytokines on Day 7 was higher in WT mice than Tg mice and correlated strongly with PPARγ expression in WT mice, but not in Tg mice. Interestingly, Tg mice showed insufficient PMN influx at 3 and 6 h, with simultaneous elevation of urinary L-FABP and reduction in HNE expression. The two strains of mice showed different types of glomerular damage, with mild mesangial proliferation in Tg mice and severe endothelial swelling with vascular thrombosis in WT mice. The glomerular damage in Tg mice was improved by administration of an ARB. The present experimental model suggests that tubular enhancement of L-FABP may protect mice with anti-GBM GN from progression of both tubulointerstitial and glomerular injury.Nephrology Dialysis Transplantation 04/2011; 26(11):3465-73. · 3.40 Impact Factor