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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 5/2013

01-10-2013 | Editorial

NK4 therapy: a new approach to target angiogenesis and inflammation in rheumatoid arthritis

Authors: Bradley J Rabquer, Alisa E Koch

Published in: Arthritis Research & Therapy | Issue 5/2013

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Abstract

Rheumatoid arthritis (RA) is a progressive autoimmune disease characterized bysynovial membrane hyperplasia, inflammation, and angiogenesis. Hepatocyte growthfactor (HGF) and its receptor, c-Met, are both overexpressed in the RA synovium.NK4 is an antagonist of HGF which has been shown to inhibit tumor growth,metastasis, and angiogenesis. In an experimental model of RA, NK4 gene therapyinhibited joint damage and inflammation in both preventative and therapeuticmodels. NK4 treatment therefore represents a possible therapeutic option incombating RA.
Literature
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Koch AE, Halloran MM, Hosaka S, Shah MR, Haskell CJ, Baker SK, Panos RJ, Haines GK, Bennett GL, Pope RM, Ferrara N: Hepatocyte growth factor. A cytokine mediating endothelial migration ininflammatory arthritis. Arthritis Rheum. 1996, 39: 1566-1575. 10.1002/art.1780390917.CrossRefPubMed
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Grandaunet B, Syversen SW, Hoff M, Sundan A, Haugeberg G, van Der Heijde D, Kvien TK, Standal T: Association between high plasma levels of hepatocyte growth factor andprogression of radiographic damage in the joints of patients with rheumatoidarthritis. Arthritis Rheum. 2011, 63: 662-669. 10.1002/art.30163.CrossRefPubMed
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Nakamura T, Sakai K, Matsumoto K: Anti-cancer approach with NK4: bivalent action and mechanisms. Anticancer Agents Med Chem. 2010, 10: 36-46. 10.2174/1871520611009010036.CrossRefPubMed
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Date K, Matsumoto K, Shimura H, Tanaka M, Nakamura T: HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocytegrowth factor. FEBS Lett. 1997, 420: 1-6. 10.1016/S0014-5793(97)01475-0.CrossRefPubMed
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Kuba K, Matsumoto K, Date K, Shimura H, Tanaka M, Nakamura T: HGF/NK4, a four-kringle antagonist of hepatocyte growth factor, is anangiogenesis inhibitor that suppresses tumor growth and metastasis inmice. Cancer Res. 2000, 60: 6737-6743.PubMed
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Sakai K, Nakamura T, Matsumoto K: Angioinhibitory action of NK4 involves impaired extracellular assembly offibronectin mediated by perlecan-NK4 association. J Biol Chem. 2009, 284: 22491-22499. 10.1074/jbc.M109.025148.PubMedCentralCrossRefPubMed
10.
Metadata
Title
NK4 therapy: a new approach to target angiogenesis and inflammation in rheumatoid arthritis
Authors
Bradley J Rabquer
Alisa E Koch
Publication date
01-10-2013
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 5/2013
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4320

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