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• W2108295655 endingPage "R73" @default.
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• W2108295655 abstract "Despite the advent of biological therapies for the treatment of rheumatoid arthritis, there is a compelling need to develop alternative therapeutic targets for nonresponders to existing treatments. Soluble receptors occur naturally in vivo, such as the splice variant of the cell surface receptor for vascular endothelial growth factor (VEGF) – a key regulator of angiogenesis in rheumatoid arthritis. Bioinformatics analyses predict that the majority of human genes undergo alternative splicing, generating proteins – many of which may have regulatory functions. The objective of the present study was to identify alternative splice variants (ASV) from cell surface receptor genes, and to determine whether the novel proteins encoded exert therapeutic activity in an in vivo model of arthritis. To identify novel splice variants, we performed RT-PCR using an mRNA pool representing major human tissue types and tumors. Novel ASV were identified by alignment of each cloned sequence to its respective genomic sequence in comparison with full-length transcripts. To test whether these ASV have biologic activity, we characterized a subset of them for ligand binding, and for efficacy in an animal model of arthritis. The in vivo study was accomplished using adenoviruses expressing secreted ASV. We cloned 60 novel human ASV from 21 genes, encoding cell surface receptors – many of which are known to be important in the regulation of angiogenesis. The ASV were characterized by exon extension, intron retention and alternative exon utilization. Efficient expression and secretion of selected ASV – corresponding to VEGF receptor type 1, VEGF receptor type 2, VEGF receptor type 3, angiopoietin receptor Tie1, Met (receptor for hepatocyte growth factor), colony-stimulating factor 1 receptor, platelet-derived growth factor receptor beta, fibroblast growth factor receptor 1, Kit, and RAGE – was demonstrated, together with binding to their cognate ligands. Importantly, ASV derived from VEGF receptor type 1 and Tie1, and to a lesser extent from VEGF receptor type 2 and fibroblast growth factor receptor 1, reduced clinical signs of arthritis in vivo. The reduction was paralleled by decreased joint inflammation and destruction. The present study shows that unique ASV derived from receptors that play key roles in angiogenesis – namely, VEGF receptor type 1 and, for the first time, Tie1 – can markedly reduce arthritis severity. More broadly, our results demonstrate that ASV are a source of novel proteins with therapeutic potential in diseases in which angiogenesis and cellular hyperplasia play a central role, such as rheumatoid arthritis." @default.
• W2108295655 created "2016-06-24" @default.
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• W2108295655 date "2008-01-01" @default.
• W2108295655 modified "2023-10-15" @default.
• W2108295655 title "Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis" @default.
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• W2108295655 cites W1597588755 @default.
• W2108295655 cites W1691912414 @default.
• W2108295655 cites W1758236490 @default.
• W2108295655 cites W1830545719 @default.
• W2108295655 cites W1873126901 @default.
• W2108295655 cites W1898477889 @default.
• W2108295655 cites W1959263913 @default.
• W2108295655 cites W1966821227 @default.
• W2108295655 cites W1970614272 @default.
• W2108295655 cites W1970668637 @default.
• W2108295655 cites W1973188134 @default.
• W2108295655 cites W1973282765 @default.
• W2108295655 cites W1974045062 @default.
• W2108295655 cites W1974661608 @default.
• W2108295655 cites W1975009096 @default.
• W2108295655 cites W1980725734 @default.
• W2108295655 cites W1982425773 @default.
• W2108295655 cites W1984095718 @default.
• W2108295655 cites W1984487339 @default.
• W2108295655 cites W1985589632 @default.
• W2108295655 cites W2000537146 @default.
• W2108295655 cites W2001935059 @default.
• W2108295655 cites W2007601317 @default.
• W2108295655 cites W2007911202 @default.
• W2108295655 cites W2008892026 @default.
• W2108295655 cites W2011415255 @default.
• W2108295655 cites W2013829686 @default.
• W2108295655 cites W2016000024 @default.
• W2108295655 cites W2020250668 @default.
• W2108295655 cites W2034672236 @default.
• W2108295655 cites W2038535814 @default.
• W2108295655 cites W2038903837 @default.
• W2108295655 cites W2039130368 @default.
• W2108295655 cites W2039279368 @default.
• W2108295655 cites W2041708393 @default.
• W2108295655 cites W2045247659 @default.
• W2108295655 cites W2048618925 @default.
• W2108295655 cites W2050061160 @default.
• W2108295655 cites W2051268134 @default.
• W2108295655 cites W2056855407 @default.
• W2108295655 cites W2066314640 @default.
• W2108295655 cites W2077689651 @default.
• W2108295655 cites W2078348571 @default.
• W2108295655 cites W2084740377 @default.
• W2108295655 cites W2085406330 @default.
• W2108295655 cites W2085853581 @default.
• W2108295655 cites W2096454490 @default.
• W2108295655 cites W2103645493 @default.
• W2108295655 cites W2104878733 @default.
• W2108295655 cites W2105669313 @default.
• W2108295655 cites W2127681935 @default.
• W2108295655 cites W2128012941 @default.
• W2108295655 cites W2131882149 @default.
• W2108295655 cites W2137986897 @default.
• W2108295655 cites W2141664715 @default.
• W2108295655 cites W2141708447 @default.
• W2108295655 cites W2151752381 @default.
• W2108295655 cites W2153324915 @default.
• W2108295655 cites W2154219696 @default.
• W2108295655 cites W2154803112 @default.
• W2108295655 cites W2163301034 @default.
• W2108295655 cites W2166841658 @default.
• W2108295655 cites W2346794077 @default.
• W2108295655 cites W2395587199 @default.
• W2108295655 cites W2418854546 @default.
• W2108295655 cites W250039085 @default.
• W2108295655 cites W45534775 @default.
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• W2108295655 doi "https://doi.org/10.1186/ar2447" @default.
• W2108295655 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2575619" @default.
• W2108295655 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18593464" @default.
• W2108295655 hasPublicationYear "2008" @default.
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