Gene expression profiles of human proximal tubular epithelial cells in proteinuric nephropathies.
In kidney disease renal proximal tubular epithelial cells (RPTEC) actively contribute to the progression of tubulointerstitial fibrosis by mediating both an inflammatory response and via epithelial-to-mesenchymal transition. Using laser capture microdissection we specifically isolated RPTEC from cryosections of the healthy parts of kidneys removed owing to renal cell carcinoma and from kidney biopsies from patients with proteinuric nephropathies. RNA was extracted and hybridized to complementary DNA microarrays after linear RNA amplification. Statistical analysis identified 168 unique genes with known gene ontology association, which separated patients from controls. Besides distinct alterations in signal-transduction pathways (e.g. Wnt signalling), functional annotation revealed a significant upregulation of genes involved in cell proliferation and cell cycle control (like insulin-like growth factor 1 or cell division cycle 34), cell differentiation (e.g. bone morphogenetic protein 7), immune response, intracellular transport and metabolism in RPTEC from patients. On the contrary we found differential expression of a number of genes responsible for cell adhesion (like BH-protocadherin) with a marked downregulation of most of these transcripts. In summary, our results obtained from RPTEC revealed a differential regulation of genes, which are likely to be involved in either pro-fibrotic or tubulo-protective mechanisms in proteinuric patients at an early stage of kidney disease.
Rudnicki
M
M
Division of Nephrology, Medical University Innsbruck, Innsbruck, Austria. michael.rudnicki@i-med.ac.at
Eder
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Perco
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Enrich
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Scheiber
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Koppelstätter
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Schratzberger
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Mayer
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Oberbauer
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Meyer
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Mayer
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D000368:Aged; D017209:Apoptosis / Q000235:genetics; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D019699:Thrombospondins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D018797:Cell Cycle Proteins; D007155:Immunologic Factors; D019699:Thrombospondins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C101863:thrombospondin 3