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Article: Sam68-like mammalian protein 2, identified by digital differential display as expressed by podocytes, is induced in proteinuria and involved in splice site selection of vascular endothelial growth factor

TitleSam68-like mammalian protein 2, identified by digital differential display as expressed by podocytes, is induced in proteinuria and involved in splice site selection of vascular endothelial growth factor
Authors
Issue Date2005
Citation
Journal of the American Society of Nephrology, 2005, v. 16 n. 7, p. 1958-1965 How to Cite?
AbstractPodocytes, the glomerular epithelial cells of the kidney, share important features with neuronal cells. In addition to phenotypical and functional similarities, a number of gene products have been found to be expressed exclusively or predominantly by both cell types. With the hypothesis of a common transcriptome shared by podocytes and neurons, digital differential display was used to identify novel podocyte-expressed gene products. Comparison of brain and kidney cDNA libraries with those of other organs identified Sam68-like mammalian protein 2 (SLM-2), a member of the STAR family of RNA processing proteins, as expressed by podocytes. SLM-2 expression was found to be restricted in the kidney to podocytes. In proteinuric diseases, SLM-2, a known regulator of neuronal mRNA splice site selection, was found significantly upregulated on mRNA and protein levels. Knockdown of SLM-2 by short interfering RNA in podocytes was performed to evaluate its biologic role. RNA splicing of vascular endothelial growth factor (VEGF), a key regulator of the filtration barrier and expressed as functionally distinct splice isoforms, was evaluated. VEGF 165 expression was found to be reduced by 25% after SLM-2 knockdown. In vivo, the glomerular expression of SLM-2 correlated with the mRNA levels of VEGF165. This study demonstrates the power of digital differential display to predict cell type-specific gene expression by hypothesis-driven analysis of tissue cDNA libraries. SLM-2-dependent VEGF splicing indicates the importance of mRNA splice site selection for glomerular filtration barrier function. Copyright © 2005 by the American Society of Nephrology.
Persistent Identifierhttp://hdl.handle.net/10722/195431
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCohen, CD-
dc.contributor.authorDoran, PP-
dc.contributor.authorBlattner, SM-
dc.contributor.authorMerkle, M-
dc.contributor.authorWang, GQ-
dc.contributor.authorSchmid, H-
dc.contributor.authorMathieson, PW-
dc.contributor.authorSaleem, MA-
dc.contributor.authorHenger, A-
dc.contributor.authorRastaldi, MP-
dc.contributor.authorKretzler, M-
dc.date.accessioned2014-02-28T06:12:08Z-
dc.date.available2014-02-28T06:12:08Z-
dc.date.issued2005-
dc.identifier.citationJournal of the American Society of Nephrology, 2005, v. 16 n. 7, p. 1958-1965-
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/195431-
dc.description.abstractPodocytes, the glomerular epithelial cells of the kidney, share important features with neuronal cells. In addition to phenotypical and functional similarities, a number of gene products have been found to be expressed exclusively or predominantly by both cell types. With the hypothesis of a common transcriptome shared by podocytes and neurons, digital differential display was used to identify novel podocyte-expressed gene products. Comparison of brain and kidney cDNA libraries with those of other organs identified Sam68-like mammalian protein 2 (SLM-2), a member of the STAR family of RNA processing proteins, as expressed by podocytes. SLM-2 expression was found to be restricted in the kidney to podocytes. In proteinuric diseases, SLM-2, a known regulator of neuronal mRNA splice site selection, was found significantly upregulated on mRNA and protein levels. Knockdown of SLM-2 by short interfering RNA in podocytes was performed to evaluate its biologic role. RNA splicing of vascular endothelial growth factor (VEGF), a key regulator of the filtration barrier and expressed as functionally distinct splice isoforms, was evaluated. VEGF 165 expression was found to be reduced by 25% after SLM-2 knockdown. In vivo, the glomerular expression of SLM-2 correlated with the mRNA levels of VEGF165. This study demonstrates the power of digital differential display to predict cell type-specific gene expression by hypothesis-driven analysis of tissue cDNA libraries. SLM-2-dependent VEGF splicing indicates the importance of mRNA splice site selection for glomerular filtration barrier function. Copyright © 2005 by the American Society of Nephrology.-
dc.languageeng-
dc.relation.ispartofJournal of the American Society of Nephrology-
dc.titleSam68-like mammalian protein 2, identified by digital differential display as expressed by podocytes, is induced in proteinuria and involved in splice site selection of vascular endothelial growth factor-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1681/ASN.2005020204-
dc.identifier.pmid15901763-
dc.identifier.scopuseid_2-s2.0-27744528827-
dc.identifier.volume16-
dc.identifier.issue7-
dc.identifier.spage1958-
dc.identifier.epage1965-
dc.identifier.isiWOS:000230046900014-

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