title: Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset.
abstract: Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-enriched gene expression dataset (REGGED) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with 'a priori' known prominent glomerular expression served for validation and were all found in the novel dataset (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression of several novel glomerulus-enriched genes in REGGED was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli of healthy human adult kidneys including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. In diabetic nephropathy, a prevalent glomerulopathy, differential regulation of glomerular ROBO2 mRNA was found.In summary, novel transcripts with predominant expression in the human glomerulus could be identified using a comparative strategy on microdissected nephrons. A systematic analysis of this glomerulus-specific gene expression dataset allows the detection of target molecules and biological processes involved in glomerular biology and renal disease.
authors.affiliation: Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Maja T
authors.initials: MT
authors.lastname: Lindenmeyer
authors.forename: Felix
authors.initials: F
authors.lastname: Eichinger
authors.forename: Kontheari
authors.initials: K
authors.lastname: Sen
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
authors.forename: Ilka
authors.initials: I
authors.lastname: Edenhofer
authors.forename: Deborah
authors.initials: D
authors.lastname: Mattinzoli
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.forename: Maria P
authors.initials: MP
authors.lastname: Rastaldi
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
mesh_terms: D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D030541:Databases, Genetic; D058851:GPI-Linked Proteins; D015870:Gene Expression; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D050199:Podocytes / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097905:Roundabout Proteins
chemical_list: D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C484539:NRN1 protein, human