File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant

TitleHeterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant
Authors
KeywordsGlomeruli
Permselectivity
Proteinuria
VEGF148
Issue Date1999
Citation
Clinical Science, 1999, v. 97 n. 3, p. 303-312 How to Cite?
AbstractVascular endothelial growth factor (VEGF) mediates increased vascular permeability and endothelial mitogenesis, and may orchestrate normal glomerular permselectivity and proteinuria. Distinct isoforms result from differential gene splicing. VEGF binds to two cell surface tyrosine-kinase receptors, KDR (kinase domain region) and Flt-1 (fms-like tyrosine kinase-1). The latter also exists in a soluble form (sFlt), which is inhibitory. We have studied patterns of VEGF-isoform and VEGF-receptor expression in isolated single normal human glomeruli. mRNA from 190 glomeruli (from 20 individuals) was harvested on to magnetic beads, and nested reverse transcription-PCR was performed using primers for the VEGF isoforms and VEGF receptors. Simultaneous nested reverse transcription-PCR for CD45 was conducted in order to exclude leucocyte contamination. Unexpected products were isolated, cloned and sequenced. Multiple patterns of glomerular VEGF mRNA isoform expression were identified. Most frequently (58%), all three common forms were expressed. VEGF189 (i.e. 189-amino-acid form of VEGF) was expressed in 63%, VEGF165 in 85% and VEGF121 in 84% of glomeruli. Two unexpected PCR products were also identified: 18% of glomeruli expressed VEGF145, and 27% of glomeruli expressed a new truncated VEGF splice variant, VEGF148, lacking exon 6, the terminal part of exon 7 and exon 8. Multiple patterns of VEGF-receptor expression were also identified, the most common being expression of all three isoforms (28%). Overall, KDR was seen in 59% of glomeruli, Flt-1 in 45% and sFlt in 57%. Thus the expression of VEGF within normal glomeruli is complex and variable, with inter- and intra-individual variation. Furthermore, sFlt appears to be the co-dominant form of VEGF receptor expressed within glomeruli, suggesting that, in healthy individuals, a degree of VEGF autoregulation is the norm. The physiological importance of VEGF148 remains to be confirmed.
Persistent Identifierhttp://hdl.handle.net/10722/195355
ISSN
2023 Impact Factor: 6.7
2023 SCImago Journal Rankings: 1.565
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWhittle, C-
dc.contributor.authorGillespie, K-
dc.contributor.authorHarrison, R-
dc.contributor.authorMathieson, PW-
dc.contributor.authorHarper, SJ-
dc.date.accessioned2014-02-28T06:12:01Z-
dc.date.available2014-02-28T06:12:01Z-
dc.date.issued1999-
dc.identifier.citationClinical Science, 1999, v. 97 n. 3, p. 303-312-
dc.identifier.issn0143-5221-
dc.identifier.urihttp://hdl.handle.net/10722/195355-
dc.description.abstractVascular endothelial growth factor (VEGF) mediates increased vascular permeability and endothelial mitogenesis, and may orchestrate normal glomerular permselectivity and proteinuria. Distinct isoforms result from differential gene splicing. VEGF binds to two cell surface tyrosine-kinase receptors, KDR (kinase domain region) and Flt-1 (fms-like tyrosine kinase-1). The latter also exists in a soluble form (sFlt), which is inhibitory. We have studied patterns of VEGF-isoform and VEGF-receptor expression in isolated single normal human glomeruli. mRNA from 190 glomeruli (from 20 individuals) was harvested on to magnetic beads, and nested reverse transcription-PCR was performed using primers for the VEGF isoforms and VEGF receptors. Simultaneous nested reverse transcription-PCR for CD45 was conducted in order to exclude leucocyte contamination. Unexpected products were isolated, cloned and sequenced. Multiple patterns of glomerular VEGF mRNA isoform expression were identified. Most frequently (58%), all three common forms were expressed. VEGF189 (i.e. 189-amino-acid form of VEGF) was expressed in 63%, VEGF165 in 85% and VEGF121 in 84% of glomeruli. Two unexpected PCR products were also identified: 18% of glomeruli expressed VEGF145, and 27% of glomeruli expressed a new truncated VEGF splice variant, VEGF148, lacking exon 6, the terminal part of exon 7 and exon 8. Multiple patterns of VEGF-receptor expression were also identified, the most common being expression of all three isoforms (28%). Overall, KDR was seen in 59% of glomeruli, Flt-1 in 45% and sFlt in 57%. Thus the expression of VEGF within normal glomeruli is complex and variable, with inter- and intra-individual variation. Furthermore, sFlt appears to be the co-dominant form of VEGF receptor expressed within glomeruli, suggesting that, in healthy individuals, a degree of VEGF autoregulation is the norm. The physiological importance of VEGF148 remains to be confirmed.-
dc.languageeng-
dc.relation.ispartofClinical Science-
dc.subjectGlomeruli-
dc.subjectPermselectivity-
dc.subjectProteinuria-
dc.subjectVEGF148-
dc.titleHeterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1042/CS19990016-
dc.identifier.pmid10464055-
dc.identifier.scopuseid_2-s2.0-0032884545-
dc.identifier.volume97-
dc.identifier.issue3-
dc.identifier.spage303-
dc.identifier.epage312-
dc.identifier.isiWOS:000082581600007-
dc.identifier.issnl0143-5221-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats