2005 Fiscal Year Final Research Report Summary
Development of a new strategy for inhibiting the progression of diabetic nephropathy- renoprotective function of liver-type fatty acid binding protein
| Project/Area Number |
16590803
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
KIMURA Kenjiro St.Marianna University School of Medicine, medical department, Professor, 医学部, 教授 (00161555)
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| Project Period (FY) |
2004 – 2005
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| Keywords | diabetic nephropathy / liver-type fatty acid binding protein / tubulointerstitial damage / biomarker / transgenic animals / urinary fatty acid / urinary albumin / early diagnosis |
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| Research Abstract |
The number of patients with Diabetic nephropathy (DN) is increasing worldwide. DN is a principal cause of kidney disease that ultimately progress to end-stage renal failure. Liver-type FABP (L-FABP) of 14.4kDa is expressed in the proximal tubule. We established a two step sandwich enzyme linked immunosorbent assay (ELISA) method for determining human L-FABP in urine. In this study, we examined the dynamics of renal L-FABP and clinical significance of urinary renal L-FABP in DN.
1)Experimental study
Because L-FABP is not expressed in murine kidneys, we established transgenic (Tg) mice with the human L-FABP gene. In streptozotocin (STZ)-induced DN model with these Tg mice, we found that the expression of L-FABP in the proximal tubules was up-regulated and urinary excretion of renal L-FABP was accelerated.
2)Clinical study
・Urinary L-FABP was measured in patients with non-insulin dependent diabetes mellitus (n=147) by ELISA using specific monoclonal antibodies. The level of urinary L-FABP was significantly increased according to the severity of DN. Furthermore, urinary L-FABP in the patients with normoalbuminuria was significantly higher than that in the normal controls (p=0.0000). Urinary L-FABP may be a useful diagnostic risk marker for progression of diabetic nephropathy.
・Urinary L-FABP was measured in patients with nephrotic syndrome due to DN (n=8) and those with minimal change nephrotic syndrome (MCNS, n=12). Urinary fatty acid (FA) and urinary L-FABP were significantly elevated in DN than compared to MCNS. The degree of tubulointerstitial damage was significantly more severe in patients with DN compared to those with MCNS. Elevated urinary excretion of FA is a reflection of FA overload in the proximal tubules and FA may be an important promoter of tubulointerstitial damage in DN patients. Urinary L-FABP reflects the FA stress to the proximal tubules, which cause severe tubulointerstitial damage.
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[Journal Article] Urinary liver-type fatty acid-binding protein as a useful biomarker in chronic kidney disease2006
Author(s)
Kamijo A, Sugaya T, Hikawa A, Yamanouchi M, Hirata Y, Ishimitsu T, Numabe A, Takagi M, Hayakawa H, Tabei F, Sugimoto T, Mise N, Omata M, Kimura K
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Journal Title
Mol Cell Biochem 284
Pages: 175-182
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease : A multicenter trial2005
Author(s)
Kamijo A, Sugaya T, Hikawa A, Yamanouchi M, Hirata Y, Ishimitsu T, Numabe A, Takagi M, Hayakawa H, Tabei F, Sugimoto T, Mise N, Kimura K
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Journal Title
J Lab Clin Med 145
Pages: 126-133
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Urinary excretion of fatty acid-binding protein reflects stress overload on the proximal tubules2004
Author(s)
Kamijo A, Sugaya T, Hikawa A, Okada M, Okumura F, Yamanouchi M, Honda A, Okabe M, Fujino T, Hirata Y, Omata M, Kaneko R, Fujii H, Fukamizu A, Kimura K.
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Journal Title
Am J Pathol. 165
Pages: 1243-1255
Description
「研究成果報告書概要(欧文)」より
