Перегляд вихідного коду сторінки Plus the relative amount of VEGFXXXb is higher in typical tissues

VEGF treatments currently & in the future Interrupting VEGF/VEGFR to reduce angiogenesis has moved into the clinic to treat a range to tumor types and eye disease, but not without varied response rates, side effects and resistance. Focusing on splicing and how this can be altered in vivo is a promising treatment target.  ~~ Administration of recombinant VEGF165b inhibits ocular angiogenesis in mouse models of retinopathy and age-related macular degeneration, and colorectal carcinoma and metastatic melanoma. Splicing aspects and their regulatory molecules alter splice site selection, such that cells can switch from the anti-angiogenic VEGFxxxb isoforms to the pro-angiogenic VEGFxxx isoforms, including SRp55, ASF/SF2 and SRPK, and inhibitors of these molecules can inhibit angiogenesis in the eye, and splice site selection in cancer cells, [http://www.tongji.org/members/jeffsalmon70/activity/233306/ http://www.tongji.org/members/jeffsalmon70/activity/233306/] opening up the possibility of using splicing factor inhibitors as novel anti-angiogenic therapeutics. Endogenous anti-angiogenic VEGFxxxb isoforms are cytoprotective for endothelial, epithelial and neuronal cells in vitro and in vivo, suggesting both an improved safety profile and an explanation for unpredicted anti-VEGF side effects. In summary, C-terminal distal splicing is a key component of VEGF biology, overlooked by the vast majority of publications in the field, and these findings require a radical revision of our understanding of VEGF biology in typical human physiology. Keywords angiogenesis; carcinoma sample; Denys-Drash syndrome; human vitreous fluid; rheumatoid arthritis; vasculogenesis VEGF -A [http://ramaaltofoula.com/members/kale31fowl/activity/482367/ http://ramaaltofoula.com/members/kale31fowl/activity/482367/] alternative splicing VEGF has become a centre of intense interest due to its essential role in neovascularization in a variety of physiological and pathological processes, such as the female reproductive cycle, wound healing, tumours, angiogenic eye diseases such as age-related macular degeneration and diabetic retinopathy, myocardial ischaemia, pre-eclampsia and rheumatoid arthritis. Angiogenesis, the process of new blood vessel formation from pre-existing blood vessels, is important in generating new blood vessels necessary to provide metabolic substrates, such as glucose and oxygen for tissues and transferring substrates for hormone synthesis for endocrine tissues/organs, as well as efficient removal of waste products as well as the distribution of hormones synthesized systemically. 2009 Biochemical Society 1 To whom correspondence should be addressed.. Qiu et al. Page 2 The VEGF gene consists of eight exons separated by seven introns and spans approx. 14 kb. The VEGF pre-RNA is differentially spliced to form two families of proteins, each of which contain multiple isoforms of varying amino acid number according to alternative inclusion of exons 6 and 7, which encode heparin-binding domains. The two families are formed by alternative 3 splice site selection in the terminal exon to give two different C-terminal sequences, and these families are termed VEGFxxx and VEGFxxxb , where xxx denotes the amino acid number. The most widely studied VEGFxxxb isoform is VEGF165b, but VEGF121b and VEGF189b have also been identified at the mRNA and protein levels. The VEGFxxxb family of isoforms is formed by distal splice site selection 66 bp downstream of the proximal splice site in exon 8 . This distal splicing event results in an open reading frame of the sa.As well as the relative degree of VEGFXXXb is higher in normal tissues and is lowered in canacer. VEGF splicing is often regulated by development things and alternative splice elements.