Nobuyuki Takahashi

Personal Information
Title Associate Professor
Expertise Nephropathy
Institution Tohoku University
Data Summary
TypeCount
Grants/SubContracts 1
Progress Reports 1
Publications 5
Protocols 1
Committees 2
Experiments 0
Strains 0
Models 0

SubContract(s)


Protease-activated receptors in diabetic complications
Diabetic nephropathy is a leading cause of renal failure and is a major life-threatening problem. Although pharmacological inhibition of the renin-angiotensin system slows progression of diabetic nephropathy, patient prognosis remains poor. We have clarified that lack or reduced expression of endothelial nitric oxide synthase (eNOS, Nos3) exacerbates diabetic nephropathy, which is associated with increased expression and activity of renal tissue factor (TF), an initiator of the coagulation cascade. Anti-TF neutralizing antibody reduced inflammation in diabetic nephropathy. Coagulation proteases contribute to tissue injury mediated by protease-activated receptors (PARs). PAR2 is activated by TF- coagulation factor VIIa (FVIIa) complex and coagulation factor Xa (FXa) and up-regulates inflammation and fibrosis. Most recently we reported that lack of PAR2 are protective against diabetic nephropathy. Interestingly, these mice have reduced PAR1 expression in the kidney. Both PAR1 and PAR2 are proinflammatory, and PAR1 is known to be increased in diabetic kidneys. Accordingly, PAR2 and possibly PAR1 are promising target for diabetic complications. Specific Aim 1 will clarify whether inhibiting both PAR1 and PAR2 is more effective in preventing diabetic nephropathy than inhibiting PAR2 alone. We generate male mice lacking PAR2 (F2rl1-/-) or having wild type PAR2 (F2rl1+/+) on Nos3+/- and Ins2Akita/+ background. These mice will be divided into two groups and treated or not treated with PAR1 specific antagonist E5555. Specific Aim 2 will identify chemical compounds with PAR2 inhibiting properties. PAR2 antagonists will be screened using several chemical compound libraries. We add library compounds and calcium sensitive dye Fluo4 to human endothelial cell line EA.hy926, and look for compounds that inhibit the increase in intracellular calcium by a PAR2 agonist peptide 2f-LIGRLO. Selectivity of the compounds for PAR2 and PAR1 will be evaluated by inhibition of the increase in intracellular calcium by a PAR1 agonist.


Progress Reports

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Protease-activated receptors in diabetic complications (Takahashi, Nobuyuki)
11/17/2017View Progress Report Document
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Annual Reports

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 PublicationAltmetricsSubmitted ByPubMed IDStatus

Year: 2012; Items: 1

 
eNOS deficiency acts through endothelin to aggravate sFlt-1-induced pre-eclampsia-like phenotype.
Li F, Hagaman JR, Kim HS, Maeda N, Jennette JC, Faber JE, Karumanchi SA, Smithies O, Takahashi N
Journal of the American Society of Nephrology : JASN, 2012 (23), 652 - 660
22282588
Published

Year: 2011; Items: 2

 
A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy.
Wang CH, Li F, Hiller S, Kim HS, Maeda N, Smithies O, Takahashi N
Proceedings of the National Academy of Sciences of the United States of America, 2011 (108), 2070 - 5
21245338
Published
 
A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy.
Wang CH, Li F, Hiller S, Kim HS, Maeda N, Smithies O, Takahashi N
Proceedings of the National Academy of Sciences of the United States of America, 2011 (108), 2070 - 2075
21245338
Published

Year: 2010; Items: 2

 
Loss of bradykinin signaling does not accelerate the development of cardiac dysfunction in type 1 diabetic akita mice.
Wende AR, Soto J, Olsen CD, Pires KM, Schell JC, Larrieu-Lahargue F, Litwin SE, Kakoki M, Takahashi N, Smithies O, Abel ED
Endocrinology, 2010 (151), 3536 - 3542
20501666
Published
 
The renin angiotensin system and the metabolic syndrome.
Wang CH, Li F, Takahashi N
The open hypertension journal, 2010 (3), 1 - 13
21132096
Published

No uploaded documents found.

No experiments found.

No strains found.

No models found.