A human glomerular SAGE transcriptome database

Nyström, Jenny; Fierlbeck, Wolfgang; Granqvist, Anna; Kulak, Stephen C.; Ballermann, Barbara J.

doi:10.1186/1471-2369-10-13

Cited by 23 publications

(21 citation statements)

References 39 publications

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“…AL049313), representing the 3= end of the CLIC5 gene, was also enriched compared with nonglomerular ECs (52). Enrichment of the CLIC5 transcript in glomeruli, which is similar to that observed for transcripts of podocytespecific proteins (44), suggests that CLIC5 might play an important functional role in the glomerulus.…”

mentioning

confidence: 67%

“…We have reported that the transcript for chloride intracellular channel 5 (CLIC5) is enriched ϳ800-fold in human glomeruli compared with pooled nonglomerular tissues and cells by serial analysis of gene expression (SAGE) (44). A similar enrichment of the CLIC5 transcript is also evident in a human glomerular SAGE library that was compared with libraries from microdissected nephron segments (13), and the CLIC5 transcript is enriched in a mouse glomerular expressed sequence tag library compared with whole kidney (27).…”

mentioning

confidence: 75%

“…A SAGE tag (CATGAATCT-GAACCAATTACC) corresponding to the 3=-UTR of the CLIC5 transcript was previously found to be predominant in renal glomeruli (44). Here, we first determined whether this SAGE tag indeed corresponds to CLIC5 and which of the two CLIC5 transcript variants predominate in kidney.…”

Section: Clic5a Mrna Expressionmentioning

confidence: 96%

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CLIC5A, a component of the ezrin-podocalyxin complex in glomeruli, is a determinant of podocyte integrity

Wegner

Al-Momany

Kulak

et al. 2010

American Journal of Physiology-Renal Physiology

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The chloride intracellular channel 5A (CLIC5A) protein, one of two isoforms produced by the CLIC5 gene, was isolated originally as part of a cytoskeletal protein complex containing ezrin from placental microvilli. Whether CLIC5A functions as a bona fide ion channel is controversial. We reported previously that a CLIC5 transcript is enriched approximately 800-fold in human renal glomeruli relative to most other tissues. Therefore, this study sought to explore CLIC5 expression and function in glomeruli. RT-PCR and Western blots show that CLIC5A is the predominant CLIC5 isoform expressed in glomeruli. Confocal immunofluorescence and immunogold electron microscopy reveal high levels of CLIC5A protein in glomerular endothelial cells and podocytes. In podocytes, CLIC5A localizes to the apical plasma membrane of foot processes, similar to the known distribution of podocalyxin and ezrin. Ezrin and podocalyxin colocalize with CLIC5A in glomeruli, and podocalyxin coimmunoprecipitates with CLIC5A from glomerular lysates. In glomeruli of jitterbug (jbg/jbg) mice, which lack the CLIC5A protein, ezrin and phospho-ERM levels in podocytes are markedly lower than in wild-type mice. Transmission electron microscopy reveals patchy broadening and effacement of podocyte foot processes as well as vacuolization of glomerular endothelial cells. These ultrastructural changes are associated with microalbuminuria at baseline and increased susceptibility to adriamycin-induced glomerular injury compared with wild-type mice. Together, the data suggest that CLIC5A is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture. We postulate that the interaction between podocalyxin and subjacent filamentous actin, which requires ezrin, is compromised in podocytes of CLIC5A-deficient mice, leading to dysfunction under unfavorable genetic or environmental conditions.

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confidence: 67%

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confidence: 75%

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CLIC5A, a component of the ezrin-podocalyxin complex in glomeruli, is a determinant of podocyte integrity

Wegner

Al-Momany

Kulak

et al. 2010

American Journal of Physiology-Renal Physiology

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“…It is expressed throughout the cytoplasm and plasma membrane of the podocyte, but is not expressed by other human glomerular cell types (Figure 1). Gene expression analysis in human kidney supports an expression pattern limited to glomeruli, and in particular, podocytes (28)(29)(30). In contrast, this podocyterestricted pattern in humans is not found in mice (31) or rats (32), where PLA 2 R is expressed by glomerular cells other than podocytes.…”

Section: Antigen Identification In Human Diseasementioning

confidence: 97%

Membranous nephropathy: from models to man

Beck¹,

Salant²

2014

J. Clin. Invest.

148

138

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As recently as 2002, most cases of primary membranous nephropathy (MN), a relatively common cause of nephrotic syndrome in adults, were considered idiopathic. We now recognize that MN is an organ-specific autoimmune disease in which circulating autoantibodies bind to an intrinsic antigen on glomerular podocytes and form deposits of immune complexes in situ in the glomerular capillary walls. Here we define the clinical and pathological features of MN and describe the experimental models that enabled the discovery of the major target antigen, the M-type phospholipase A 2 receptor 1 (PLA 2 R). We review the pathophysiology of experimental MN and compare and contrast it with the human disease. We discuss the diagnostic value of serological testing for anti-PLA 2 R and tissue staining for the redistributed antigen, and their utility for differentiating between primary and secondary MN, and between recurrent MN after kidney transplant and de novo MN. We end with consideration of how knowledge of the antigen might direct future therapeutic strategies.

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“…14,15 The kidney is a key organ for BP regulation and the site of highest FGF1 expression (http://www.proteinatlas.org/ ENSG00000113578/tissue). FGF1 is one of the glomerulusenriched genes [16][17][18][19] and previous immunochemistry confirmed the exclusive expression of FGF1 within apparently normal human glomeruli. 6,20 A number of mRNAs (i.e., Nephrosis 1, congenital, Finnish type [nephrin] gene, NPHS1; Nephrosis 2, idiopathic, steroid-resistant [podocin] gene, NPHS2) most tightly coexpressed with FGF1 in kidneys examined here are known as key structural constituents of the glomerulus.…”

Section: Discussionmentioning

confidence: 98%

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

Tomaszewski

Eales

Denniff

et al. 2015

Journal of the American Society of Nephrology

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The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65310 25) and diastolic BP (P=7.61310 23) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0310 23). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, reninangiotensin cascade, and sodium handling network may explain the association between FGF1 and BP. Essential hypertension is a net product of genetic factors and environmental exposure acting together on regulatory systems in key organs for BP homeostasis. The kidney is central to BP regulation and drives the development of hypertension through numerous mechanisms including glomerular hemodynamics, tubular reabsorption of sodium, actions of the renin-angiotensin system, and natriuretic peptides. 1 Rare genetic variants that affect expression of molecules and pathways operating within the kidney lead to elevated BP in monogenic forms of hypertension. 2 Several common variants in genes associated with BP and/or susceptibility to hypertension are also believed to act through the

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A human glomerular SAGE transcriptome database

Cited by 23 publications

References 39 publications

CLIC5A, a component of the ezrin-podocalyxin complex in glomeruli, is a determinant of podocyte integrity

CLIC5A, a component of the ezrin-podocalyxin complex in glomeruli, is a determinant of podocyte integrity

Membranous nephropathy: from models to man

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

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