Molecular identification of the liver- and the heart-type fatty acid-binding proteins in human and rat kidney. Use of the reverse transcriptase polymerase chain reaction

Maatman, R.; Westerlo, Els M.A. van de; Kuppevelt, T. H. M. S. M. Van; Veerkamp, J.H.

doi:10.1042/bj2880285

Cited by 128 publications

(88 citation statements)

References 34 publications

(24 reference statements)

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“…There was a discrepancy in previous studies on the localization of L-FABP in the mammalian kidney in that L-FABP was localized in PTC and DTC in the rat kidney, 14 but only in PTC in the human kidney. 13 We performed immunohistochemical analyses for the distribution of L-FABP in the rat kidney.…”

Section: L-fabp Is Localized In the Lysosomes Of Rat Ptccontrasting

confidence: 41%

“…The finding is compatible with a previous report on the low mRNA expression of L-FABP both in the human and rat kidney. 14 In rats that had been treated with different doses of CCl 4 , the level of L-FABP mRNA expression in the kidney was low and did not differ from that in the kidney of control rats (Figure 2b). These results suggest that renal L-FABP synthesis is very low and that there may be a pathway to transport L-FABP to the kidney via the circulation.…”

Section: L-fabp Is Localized In the Lysosomes Of Rat Ptcmentioning

confidence: 99%

“…13 However, in the rat kidney, L-FABP was detected not only in PTC but also in distal tubule cells (DTC). 14 Moreover, the precise subcellular localization of L-FABP in the kidney, and the origin and functions of renal L-FABP are not known. L-FABP is putatively involved in the renal metabolism of FFA, which are major substrates for oxidation in the renal cortex [15][16][17] but have harmful effects on the kidney in nephrotic conditions.…”

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confidence: 99%

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Evidence for megalin-mediated proximal tubular uptake of L-FABP, a carrier of potentially nephrotoxic molecules

Oyama

Takeda

Hama

et al. 2005

Laboratory Investigation

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Liver-type fatty acid binding protein (L-FABP) binds with high affinity to hydrophobic molecules including free fatty acid, bile acid and bilirubin, which are potentially nephrotoxic, and is involved in their metabolism mainly in hepatocytes. L-FABP is released into the circulation, and patients with liver damage have an elevated plasma L-FABP level. L-FABP is also present in renal tubules; however, the precise localization of L-FABP and its potential role in the renal tubules are not known. In this study, we examined the cellular and subcellular localization of L-FABP in the rat kidney and tried to determine from where the L-FABP in kidney tissues had originated. Immunohistochemical studies of kidney sections localized L-FABP in the lysosomes of proximal tubule cells (PTC). In rats with carbon tetrachloride (CCl 4 )-induced acute liver injury, we detected high levels of L-FABP in the circulation and in the kidney compared with those in the control rat by immunoblotting, while reverse transcription-polymerase chain reaction showed that the level of L-FABP mRNA expression in the kidney of CCl 4 -treated rats was low and did not differ from that in the control rat. When 35 S-L-FABP was intravenously administered to rats, the kidneys took up 35 S-L-FABP more preferentially than the liver and heart, and histoautoradiography of kidney sections revealed that 35 S-L-FABP was internalized via the apical domains of PTC. Quartz-crystal microbalance analysis revealed that L-FABP bound to megalin, a multiligand endocytotic receptor on PTC, in a Ca 2 þ -dependent manner. Degradation assays using megalin-expressing rat yolk sac tumor-derived L2 cells demonstrated that megalin mediated the cellular uptake and catabolism of 125 I-L-FABP. In conclusion, circulatory L-FABP was found to be filtered by glomeruli and internalized by PTC probably via megalin-mediated endocytosis. These results suggest a novel renal uptake pathway for L-FABP, a carrier of hydrophobic molecules, some of which may exert nephrotoxic effects.

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Section: L-fabp Is Localized In the Lysosomes Of Rat Ptccontrasting

confidence: 41%

Section: L-fabp Is Localized In the Lysosomes Of Rat Ptcmentioning

confidence: 99%

mentioning

confidence: 99%

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Evidence for megalin-mediated proximal tubular uptake of L-FABP, a carrier of potentially nephrotoxic molecules

Oyama

Takeda

Hama

et al. 2005

Laboratory Investigation

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“…4,5 L-FABP is expressed in the human proximal tubules of the kidney. 6,7 human L-FABP (hL-FABP) binds fatty acids and transports them to mitochondria or peroxisomes, where fatty acids are ␤-oxidized, and participates in intracellular fatty acid homeostasis. 8,9 Some experimental studies of animal models of kidney disease with tubulointerstitial damage revealed that renal hL-FABP was up-regulated and urinary excretion of hL-FABP was increased.…”

mentioning

confidence: 99%

Urinary Excretion of Liver Type Fatty Acid Binding Protein Accurately Reflects the Degree of Tubulointerstitial Damage

Yokoyama

Kamijo‐Ikemori

Sugaya

et al. 2009

The American Journal of Pathology

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To investigate the relationship between liver-type fatty acid-binding protein (L-FABP), a biomarker of chronic kidney disease, in the kidney and the degree of tubulointerstitial damage, folic acid (FA)-induced nephropathy was studied in a mouse model system. As renal L-FABP is not expressed in wild-type mice, human L-FABP (hL-FABP) transgenic mice were used in this study. hL-FABP is expressed in the renal proximal tubules of the transgenic mice that were injected intraperitoneally with FA in NaHCO 3 (the FA group) or only NaHCO 3 (the control group) and oral saline solution daily during the experimental period. The FA group developed severe tubulointerstitial damage with the infiltration of macrophages and the deposition of type I collagen on days 3 and 7 and recovered to the control level on day 14. The gene and protein expression levels of hL-FABP in the kidney were significantly enhanced on days 3 and 7. Urinary hL-FABP in the FA group was elevated on days 3 and 7 and decreased to the control level on day 14. The protein expression levels of hL-FABP in both the kidney and urine significantly correlated with the degree of tubulointerstitial damage, the infiltration of macrophages, and the deposition of type I collagen. In conclusion, renal expression and urinary excretion of hL-FABP significantly reflected the severity of tubulointerstitial damage in FA-induced nephropathy.

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“…6 Liver-type fatty acid-binding protein (L-FABP) is a 14-kDa protein found in the cytoplasm of human PTCs. 7 Fatty acids are bound to L-FABP and transported to the mitochondria or peroxisomes, where they are β-oxidized. This reaction plays a role in fatty acid homeostasis.…”

mentioning

confidence: 99%

Amelioration of Angiotensin II–Induced Salt-Sensitive Hypertension by Liver-Type Fatty Acid–Binding Protein in Proximal Tubules

Osaki

Suzuki²,

Sugaya³

et al. 2013

Hypertension

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Abstract-Inappropriate activation of the intrarenal renin-angiotensin system induces generation of reactive oxygen species and tubulointerstitial inflammation, which contribute to salt-sensitive hypertension (SSHT). Liver-type fatty acid-binding protein is expressed in proximal tubules in humans, but not in rodents, and may play an endogenous antioxidative role. The objective of the present study was to examine the antioxidative effect of liver-type fatty acid-binding protein on post-angiotensin II SSHT model in transgenic mice with selective overexpression of human liver-type fatty acid-binding protein in the proximal tubules. The transgenic mice showed marked protection against angiotensin II-induced SSHT.Overexpression of tubular liver-type fatty acid-binding protein prevented intrarenal T-cell infiltration and also reduced reactive oxygen species generation, intrarenal renin-angiotensin system activation, and monocyte chemotactic protein-1 expression. We also performed an in vitro study using the murine proximal tubular cell lines with or without recombinant liver-type fatty acid-binding protein and murine proximal tubular cell lines transfected with human liver-type fatty acid-binding protein, and found that gene transfection of liver-type fatty acid-binding protein and, in part, recombinant liver-type fatty acid-binding protein administration had significantly attenuated angiotensin II-induced reactive oxygen species generation and the expression of angiotensinogen and monocyte chemotactic protein-1 in murine proximal tubular cell lines. These findings indicated that liver-type fatty acid-binding protein in the proximal tubules may protect against angiotensin II-induced SSHT by attenuating activation of the intrarenal renin-angiotensin system and reducing oxidative stress and tubulointerstitial inflammation. Present data suggest that liver-type fatty acid-binding protein in the proximal tubules may be a novel therapeutic target for SSHT. 14 The expression of renal hL-FABP is upregulated in the pathological conditions in these mice, with tubulointerstitial inflammation and fibrosis being markedly attenuated compared with wild-type (WT) mice.12,14 However, the pathophysiological significance of tubular hL-FABP in local RAS activation and subsequent SSHT remains to be determined. The present study analyzed AngII-induced SSHT in hL-FABPTg mice and investigated the underlying mechanism in PTCs with or without hL-FABP transfection or treatment of recombinant L-FABP peptides (rhL-FABP). MethodsA detailed description of all methods is presented in the online-only Data Supplement. Results AngII-Induced SSHT Was Prevented in hL-FABPTg MiceAll groups had the same level of systolic blood pressure (SBP; 102-112 mm Hg) at the beginning of the study (Figure 1). AngII infusion in the WT mice induced a progressive increase in SBP (159.1±13.7 and 177.2±10.7 mm Hg at weeks 2 and 4, respectively; P<0.001 versus WT before and AngII hL-FABPTg at week 4; Figure 1). However, AngII infusion in hL-FABPTg mice induced a small incre...

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Molecular identification of the liver- and the heart-type fatty acid-binding proteins in human and rat kidney. Use of the reverse transcriptase polymerase chain reaction

Cited by 128 publications

References 34 publications

Evidence for megalin-mediated proximal tubular uptake of L-FABP, a carrier of potentially nephrotoxic molecules

Evidence for megalin-mediated proximal tubular uptake of L-FABP, a carrier of potentially nephrotoxic molecules

Urinary Excretion of Liver Type Fatty Acid Binding Protein Accurately Reflects the Degree of Tubulointerstitial Damage

Amelioration of Angiotensin II–Induced Salt-Sensitive Hypertension by Liver-Type Fatty Acid–Binding Protein in Proximal Tubules

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