Limits...
Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset.

Lindenmeyer MT, Eichinger F, Sen K, Anders HJ, Edenhofer I, Mattinzoli D, Kretzler M, Rastaldi MP, Cohen CD - PLoS ONE (2010)

Bottom Line: This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus.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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.

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.

Show MeSH

Related in: MedlinePlus

Glomerular mRNA expression of NRN1, ROBO1 and 2 mRNA in human DN, NSC, FSGS and MGN.Levels of mRNA for NRN1 (A), ROBO1 (B) and ROBO2 (C) were quantified in microdissected glomeruli from controls (n = 8), patients with established DN (DN, n = 14), NSC (n = 14), FSGS (FSGS, n = 17) and from patients with MGN (n = 17). ROBO2 was significantly down-regulated in diabetic nephropathy compared to control samples as indicated by the respective p-value, while ROBO1 and NRN1 showed no regulation. The graphs show expression ratios of each gene normalized to hGAPDH.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2902524&req=5

pone-0011545-g007: Glomerular mRNA expression of NRN1, ROBO1 and 2 mRNA in human DN, NSC, FSGS and MGN.Levels of mRNA for NRN1 (A), ROBO1 (B) and ROBO2 (C) were quantified in microdissected glomeruli from controls (n = 8), patients with established DN (DN, n = 14), NSC (n = 14), FSGS (FSGS, n = 17) and from patients with MGN (n = 17). ROBO2 was significantly down-regulated in diabetic nephropathy compared to control samples as indicated by the respective p-value, while ROBO1 and NRN1 showed no regulation. The graphs show expression ratios of each gene normalized to hGAPDH.

Mentions: To investigate intrarenal disease associated regulation of NRN1, ROBO1 and ROBO2 mRNA, we assessed the renal expression on microdissected glomeruli of cohorts with diabetic nephropathy (DN), nephrosclerosis (NSC), focal-segmental glomerulosclerosis (FSGS), membranous glomerulonephropathy (MGN) and pretransplant biopsies. Compared to normal glomeruli obtained from living donors we found a significantly lower expression of ROBO2 mRNA in DN and a trend towards a decreased expression in FSGS patients. ROBO1 and NRN1 mRNA showed no significant change in the disease cohorts (Figure 7).


Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset.

Lindenmeyer MT, Eichinger F, Sen K, Anders HJ, Edenhofer I, Mattinzoli D, Kretzler M, Rastaldi MP, Cohen CD - PLoS ONE (2010)

Glomerular mRNA expression of NRN1, ROBO1 and 2 mRNA in human DN, NSC, FSGS and MGN.Levels of mRNA for NRN1 (A), ROBO1 (B) and ROBO2 (C) were quantified in microdissected glomeruli from controls (n = 8), patients with established DN (DN, n = 14), NSC (n = 14), FSGS (FSGS, n = 17) and from patients with MGN (n = 17). ROBO2 was significantly down-regulated in diabetic nephropathy compared to control samples as indicated by the respective p-value, while ROBO1 and NRN1 showed no regulation. The graphs show expression ratios of each gene normalized to hGAPDH.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902524&req=5

pone-0011545-g007: Glomerular mRNA expression of NRN1, ROBO1 and 2 mRNA in human DN, NSC, FSGS and MGN.Levels of mRNA for NRN1 (A), ROBO1 (B) and ROBO2 (C) were quantified in microdissected glomeruli from controls (n = 8), patients with established DN (DN, n = 14), NSC (n = 14), FSGS (FSGS, n = 17) and from patients with MGN (n = 17). ROBO2 was significantly down-regulated in diabetic nephropathy compared to control samples as indicated by the respective p-value, while ROBO1 and NRN1 showed no regulation. The graphs show expression ratios of each gene normalized to hGAPDH.
Mentions: To investigate intrarenal disease associated regulation of NRN1, ROBO1 and ROBO2 mRNA, we assessed the renal expression on microdissected glomeruli of cohorts with diabetic nephropathy (DN), nephrosclerosis (NSC), focal-segmental glomerulosclerosis (FSGS), membranous glomerulonephropathy (MGN) and pretransplant biopsies. Compared to normal glomeruli obtained from living donors we found a significantly lower expression of ROBO2 mRNA in DN and a trend towards a decreased expression in FSGS patients. ROBO1 and NRN1 mRNA showed no significant change in the disease cohorts (Figure 7).

Bottom Line: This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus.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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.

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.

Show MeSH
Related in: MedlinePlus