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Differentiated human podocytes endogenously express an inhibitory isoform of vascular endothelial growth factor (VEGF(165)b) mRNA and protein
Cui, TG; Foster, RR; Saleem, M; Mathieson, PW; Gillatt, DA; Bates, DO; Harper, SJ
关键词angiogenesis small-interference RNA splicing
刊名AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
2004-04-01
DOI10.1152/ajprenal.00337.2003
286期:4页:F767-F773
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Physiology ; Urology & Nephrology
研究领域[WOS]Physiology ; Urology & Nephrology
关键词[WOS]GLOMERULAR EPITHELIAL-CELLS ; IN-SITU HYBRIDIZATION ; SPLICE VARIANT ; FACTOR VEGF ; PERMEABILITY ; KIDNEY ; NEUROPILIN-1 ; ANGIOGENESIS ; ANTIBODIES ; CARCINOMA
英文摘要

Despite production by podocytes of the proangiogenic molecule vascular endothelial growth factor-A (VEGF), the glomeruli are not sites of angiogenesis. We recently described mRNA expression of an inhibitory splice variant of VEGF (VEGF(165)b) in normal kidney (Bates DO, Cui TG, Doughty JM, Winkler M, Sugiono M, Shields JD, Peat D, Gillatt D, and Harper SJ. Cancer Res 62: 4123 - 4131, 2002). Available anti-VEGF antibodies do not distinguish stimulatory from inhibitory VEGF families. To assess the production of VEGF(165) ( stimulatory) and VEGF(165)b (inhibitory) isoforms by human podocytes, we examined both primary cultured and conditionally immortalized human podocytes using family- and isoform-specific RT-PCR. In addition, VEGF protein production was analyzed in podocytes, using isoform-specific double-strand small-interference RNAs ( siRNA). RT-PCR demonstrated the production of VEGF(189) mRNA by podocytes of both phenotypes. In contrast, on differentiation there was a splicing change from VEGF(165) to VEGF(165)b mRNA. In addition, VEGF protein in the supernatant of conditionally immortalized, differentiated podocytes was reduced by VEGF(165)b siRNA to 20 +/- 11% of the level of mock-transfected cells (P < 0.01). No reduction was seen with mismatch siRNA. Moreover, there was no reduction in VEGF protein concentration in the supernatant of primary cultured, dedifferentiated human podocytes (109 +/- 8% of mismatch siRNA, P > 0.1). In conclusion, differentiated but not dedifferentiated human podocytes secrete significant amounts of VEGF(165)b protein. It is possible that this may explain the paradox of high VEGF production in the glomerulus but no angiogenesis. Furthermore, the existence of this splicing switch in relation to podocyte phenotype suggests that alternative splicing of the VEGF pre-RNA is a regulated process that is open to manipulation and therefore could be a target for novel cancer therapies.

语种英语
WOS记录号WOS:000220033100021
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被引频次:72[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65711
专题北京大学第一临床医学院_肾脏内科
作者单位1.Univ Bristol, Dept Physiol, Preclin Vet Sch, Microvasc Res Labs, Bristol BS2 8EJ, Avon, England
2.Univ Bristol, Childrens Unit, Bristol BS8 1TH, Avon, England
3.Univ Bristol, Acad Renal Unit, Bristol BS8 1TH, Avon, England
4.Southmead Gen Hosp, Bristol Urol Inst, Bristol BS10 5NB, Avon, England
5.Beijing Univ, Teaching Hosp 1, Inst Nephrol, Beijing 10034, Peoples R China
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Cui, TG,Foster, RR,Saleem, M,et al. Differentiated human podocytes endogenously express an inhibitory isoform of vascular endothelial growth factor (VEGF(165)b) mRNA and protein[J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,2004,286(4):F767-F773.
APA Cui, TG.,Foster, RR.,Saleem, M.,Mathieson, PW.,Gillatt, DA.,...&Harper, SJ.(2004).Differentiated human podocytes endogenously express an inhibitory isoform of vascular endothelial growth factor (VEGF(165)b) mRNA and protein.AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,286(4),F767-F773.
MLA Cui, TG,et al."Differentiated human podocytes endogenously express an inhibitory isoform of vascular endothelial growth factor (VEGF(165)b) mRNA and protein".AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 286.4(2004):F767-F773.
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