Abstract |
Podocytes, 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 VEGF(165). 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.
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Authors | Clemens D Cohen, Peter P Doran, Simone M Blattner, Monika Merkle, Guo Q Wang, Holger Schmid, Peter W Mathieson, Moin A Saleem, Anna Henger, Maria P Rastaldi, Matthias Kretzler |
Journal | Journal of the American Society of Nephrology : JASN
(J Am Soc Nephrol)
Vol. 16
Issue 7
Pg. 1958-65
(Jul 2005)
ISSN: 1046-6673 [Print] United States |
PMID | 15901763
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Khdrbs3 protein, mouse
- RNA, Messenger
- RNA, Small Interfering
- RNA-Binding Proteins
- Vascular Endothelial Growth Factor A
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Topics |
- Animals
- Cell Line
- Epithelial Cells
(physiology)
- Gene Expression Profiling
- Gene Library
- Humans
- Kidney Glomerulus
(cytology, physiology)
- Mice
- Proteinuria
(metabolism)
- RNA Splicing
- RNA, Messenger
- RNA, Small Interfering
- RNA-Binding Proteins
(biosynthesis, genetics, isolation & purification)
- Transfection
- Vascular Endothelial Growth Factor A
(physiology)
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