Urinary L-type fatty acid-binding protein can reflect renal tubulointerstitial injury.
This study aimed to elucidate the role of L-type fatty acid-binding protein (L-FABP) in renal tubulointerstitial injury using a mouse adenine-induced renal injury model. C57BL/6 mice fed excess dietary adenine for 6 weeks showed a gradual increase in levels of blood urea nitrogen (BUN). They also showed severe tubulointerstitial pathological findings, such as fibrosis and macrophage infiltration without glomerular damage, which were attenuated by treatment with either allopurinol or Y-700, a new xanthine dehydroxygenase inhibitor. Because renal expression of L-FABP is defective in C57BL/6 mice, human L-FABP transgenic mice were fed an adenine-containing diet. Transgenic mice showed lower BUN levels and lower levels of pathological injury compared with wild-type mice. On the other hand, urinary levels and renal expression of L-FABP in the adenine group was significantly increased and attenuated by treatment with either allopurinol or Y-700. Urinary L-FABP was positively correlated with BUN levels and pathological damages in the tubulointerstitium. No increases in urinary protein, albumin, or N-acetyl-beta-D-glucosaminidase levels were found for 6 weeks in any group. In conclusion, we demonstrated that urinary L-FABP levels can be used to monitor both dynamics and drug responses in a mouse adenine-induced tubulointerstitial injury model.
Tanaka
Tamami
T
Department of Nephrology and Endocrinology, University Hospital, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
Doi
Kent
K
Maeda-Mamiya
Rui
R
Negishi
Kousuke
K
Portilla
Didier
D
Sugaya
Takeshi
T
Fujita
Toshiro
T
Noiri
Eisei
E
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers / Q000652:urine; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000652:urine*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000652:urine*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011720:Pyrazoles / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
C433950:1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid; D015415:Biomarkers; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; C493320:Fabp1 protein, mouse; D050556:Fatty Acid-Binding Proteins; D011720:Pyrazoles; D053773:Transforming Growth Factor beta1; D000493:Allopurinol