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Targeting Neuromedin S as a novel therapy for advanced diabetic kidney disease

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Data Summary

Applicant	Li, Jinhua
E-Mail Address	jinhua.li@monash.edu
Project Title	Targeting Neuromedin S as a novel therapy for advanced diabetic kidney disease
CBU ID	15GHSU2485
External SubContract ID	25034-64
Diabetic Complication	Nephropathy
Funding Program Group	Pilot & Feasibility [PF2015]
Abstract	Currently the management of diabetic kidney disease focuses on the treatment of hyperglycemia and high blood pressure. Clinical trials intensifying the management of glycemia or maximal treatment of high blood pressure have not decreased the risk of death or end-stage renal disease (ESRD), suggesting that other mechanism(s) may be involved in the pathogenesis of diabetic kidney disease and that new therapeutic agents are urgently needed. In a proteomic and microarray screen, we identified neuromedin s (NMS) 鈥� a poorly characterised neuropeptide - as a major factor secreted by injured endothelial cells that can directly cause podocyte injury and enhance TGF-脽1-induced activation of renal fibroblasts in vitro. Our subsequent studies identified marked up-regulation of NMS production by endothelial cells in human and experimental diabetic kidney disease. Furthermore, our exciting preliminary data shows that NMS deficient (NMS-/-) mice are significantly protected from renal interstitial fibrosis in the unilateral ureteral obstruction (UUO) model - the first study to identify a role for NMS in tissue fibrosis. In addition, we have generated a neutralising mouse anti-mouse NMS antibody (a-NMS Ab) for use as a pharmacologic NMS inhibitor. Administration of a-NMS Ab significantly decreases renal interstitial fibrosis in UUO. NMS is strongly upregulated in renal endothelial cells in advanced diabetic renal disease in a type II diabetes model, eNOS-/-db/db mice. Based on our compelling preliminary data, we hypothesis that NMS is a novel mediator of progressive diabetic kidney disease through inducing podocyte damage and promoting renal fibrosis. We will test whether administration of anti-NMS Ab will retard or even reverse the development and progression of diabetic nephropathy in type 2 diabetes model, eNOS-/-db/db mice. In addition, the direct effect of NMS on podocytes and mesangial cells will be investigated in vitro. This project will provide a major advance in our understanding of the role of NMS in the induction and progression of diabetic renal disease. The positive results will have clear translational potential as a new therapy for diabetic nephropathy, as well as for other diabetic complications.
Application PDF	Application Research Plan
Status	Contract Executed
Key Personnel
Salary Total Costs	55991
Supply Total Costs	26966
Equipment Total Costs	0
Travel/Other Total Costs	0
Direct Costs	82957
Indirect Costs Proposed	6634
Total Costs Proposed	89591
Total Costs Approved	89591
Start Date	10/1/2015
End Date	9/30/2016
IFO Name	Chibert, Joel
IFO E-Mail Address	Joel.Chibert@monash.edu
IACUC/IRB No.	99999
IACUC/IRB Institution	Monash University
Entity ID No.	98-0446326
Report Request Date	10/30/2016
T1D	NO

Type	Count
Invoices	2
Progress Reports	1

Data Submission

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Url	CBU ID	External ID	Institution	Date	Direct	Indirect	Invoice	Balance	PDF
View	15GHSU2485	25034-64	Monash University	5/1/2017	$31,414.00	-	$31,414.00	$1.00	View PDF
View	15GHSU2485	25034-64	Monash University	10/27/2016	$58,176.00	-	$58,176.00	$1.00	View PDF

Author	Complete Date	Report
Li, Jinhua	10/31/2016	View Progress Report Document

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