Gudmap

McMahon, Andrew P.; Aronow, Bruce J.; Davidson, Duncan; Davies, Jamie A.; Gaido, Kevin W.; Grimmond, Sean M.; Lessard, James L.; Little, Melissa H.; Potter, S. Steven; Wilder, Elizabeth L.; Zhang, Pumin

doi:10.1681/asn.2007101078

Cited by 240 publications

(199 citation statements)

References 15 publications

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“…Expression of these proteins in the human kidney and their phosphorylation at extracellular residues has also been observed in prior studies (51)(52)(53); however, the significance of their increased phosphorylation as observed in cell lysates is unknown and should be addressed in future studies.…”

Section: Discussionmentioning

confidence: 55%

Angiotensin II regulates phosphorylation of actin‐associated proteins in human podocytes

et al. 2017

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Within the kidney, angiotensin II (AngII) targets different cell types in the vasculature, tubuli, and glomeruli. An important part of the renal filtration barrier is composed of podocytes with their actin-rich foot processes. In this study, we used stable isotope labeling with amino acids in cell culture coupled to mass spectrometry to characterize relative changes in the phosphoproteome of human podocytes in response to short-term treatment with AngII. In 4 replicates, we identified a total of 17,956 peptides that were traceable to 2081 distinct proteins. Bioinformatic analyses revealed that among the increasingly phosphorylated peptides are predominantly peptides that are related to actin filaments, cytoskeleton, lamellipodia, mammalian target of rapamycin, and MAPK signaling. Among others, this screening approach highlighted the increased phosphorylation of actin-bundling protein, L-plastin (LCP1). AngII-dependent phosphorylation of LCP1 in cultured podocytes was mediated by the kinases ERK, p90 ribosomal S6 kinase, PKA, or PKC. LCP1 phosphorylation increased filopodia formation. In addition, treatment with AngII led to LCP1 redistribution to the cell margins, membrane ruffling, and formation of lamellipodia. Our data highlight the importance of AngII-triggered actin cytoskeleton-associated signal transduction in

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Section: Discussionmentioning

confidence: 55%

Angiotensin II regulates phosphorylation of actin‐associated proteins in human podocytes

et al. 2017

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“…In contrast to humans, where podocyte-specific microdissection is technically infeasible, murine transgenic model systems have been developed by the GenitoUrinary Development Molecular Anatomy Project (GUDMAP) consortium specifically to define celllineage-specific genes (McMahon et al 2008). Lineage tracing was established by GFP expression using cell-type-specific promoters, followed by FACS and genome-wide expression profiling of GFPpositive single-cell suspension (Brunskill et al 2011).…”

Section: Defining Cell-type-specific Transcriptionmentioning

confidence: 99%

“…Lineage tracing was established by GFP expression using cell-type-specific promoters, followed by FACS and genome-wide expression profiling of GFPpositive single-cell suspension (Brunskill et al 2011). Using the podocyte, mesangial, and endothelial cell-lineage-specific GUDMAP expression data sets (Supplemental Table 5), we subtracted endothelial and mesangial gene expression profiles from the transcriptome obtained from the podocyte preparation and identified 102 podocyte-specific transcripts (Methods; Supplemental Table 6; McMahon et al 2008). These transcripts underwent the same cell-lineage-specific evaluation in HPA as the in silico nanodissected human transcripts.…”

Section: Defining Cell-type-specific Transcriptionmentioning

confidence: 99%

Defining cell-type specificity at the transcriptional level in human disease

et al. 2013

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Cell-lineage–specific transcripts are essential for differentiated tissue function, implicated in hereditary organ failure, and mediate acquired chronic diseases. However, experimental identification of cell-lineage–specific genes in a genome-scale manner is infeasible for most solid human tissues. We developed the first genome-scale method to identify genes with cell-lineage–specific expression, even in lineages not separable by experimental microdissection. Our machine-learning–based approach leverages high-throughput data from tissue homogenates in a novel iterative statistical framework. We applied this method to chronic kidney disease and identified transcripts specific to podocytes, key cells in the glomerular filter responsible for hereditary and most acquired glomerular kidney disease. In a systematic evaluation of our predictions by immunohistochemistry, our in silico approach was significantly more accurate (65% accuracy in human) than predictions based on direct measurement of in vivo fluorescence-tagged murine podocytes (23%). Our method identified genes implicated as causal in hereditary glomerular disease and involved in molecular pathways of acquired and chronic renal diseases. Furthermore, based on expression analysis of human kidney disease biopsies, we demonstrated that expression of the podocyte genes identified by our approach is significantly related to the degree of renal impairment in patients. Our approach is broadly applicable to define lineage specificity in both cell physiology and human disease contexts. We provide a user-friendly website that enables researchers to apply this method to any cell-lineage or tissue of interest. Identified cell-lineage–specific transcripts are expected to play essential tissue-specific roles in organogenesis and disease and can provide starting points for the development of organ-specific diagnostics and therapies.

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“…We hypothesize that increased urinary excretion of both MCP-1 and CD14 in preterm infants may reflect increased risk of early renal fibrosis and its long-term consequences. Although both MCP-1 and CD14 genes are expressed in the developing murine kidney (24), their function within the developing kidney has not been established. Siglec-5 is a large cell-surface receptor (61 kDa) and member of the immunoglobulin superfamily (25).…”

Section: Articlesmentioning

confidence: 99%

“…Renal expression of Siglec-5 and its potential function in renal development is entirely unknown. There is no gene expression data regarding Siglec-5 in the GUDMAP database (24).…”

Section: Articlesmentioning

confidence: 99%

Evolution of the urinary proteome during human renal development and maturation: variations with gestational and postnatal age

et al. 2012

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Background: Low birth weight is associated with deficits in nephron number in the infant kidney and increased risk of adulthood hypertension and renal dysfunction. Urinary biomarkers may be potential indicators of renal reserve, but little is known about the influence of gestational and postnatal age on the expression of urinary proteins. The aims of this study were to determine the relationships between selected urinary proteins and renal maturation. We hypothesized that urinary protein patterns would change over time during late nephrogenesis and renal maturation. Methods: Urine samples were collected at birth and over 12 mo from preterm (33-35 wk) and term (38-40 wk) infants. candidate urinary proteins were identified by antibody array and quantified with enzyme-linked immunosorbent assay. results: Preterm infants at birth were found to have relatively elevated levels of insulin-like growth factor binding protein-1, -2, and -6, monocyte chemotactic protein-1, cD14, and sialic acid-binding Ig-like lectin 5. These markers gradually decline to levels similar to those of full-term infants by 2-6 mo of life. In contrast, many urinary markers in healthy full-term infants remain stable over the first year of life. conclusion: Gestational and postnatal age must be considered when evaluating the utility of urinary biomarkers. P remature infants are challenged to adapt to an ex utero environment while organogenesis remains incomplete. In humans, ~60% of nephrons develop during the third trimester (1) with nephrogenesis complete at 32-36 wk gestation (2). Although the kidney continues to mature for an additional 1-2 y, full-term infants have a complete endowment of nephrons, varying widely from 250,000 to 1.8 million per kidney, by 36 wk gestation (2,3) and do not form new nephrons after birth. However, the duration of nephrogenesis and the health of the nephrons in infants born prematurely remain unknown. There appears to be a correlation between gestational age and nephron number in large animal species. Studies in baboons demonstrate a direct correlation between gestational age and nephron number (4). Moreover, prematurely delivered baboons continue to develop nephrons after birth, but the length of gestation inversely correlates with the number of abnormal nephrons (4) (the lower the gestational age the higher the number of abnormal nephrons). There may be a limited window for nephrogenesis to continue postnatally in humans. A single autopsy study has shown that nephrogenesis appears to continue for 40 postnatal days in extremely preterm human infants and then cease (5). A smaller complement of nephrons may not be reflected by renal dysfunction in the preterm infant. However, adults born at a low birth weight, with a reduced number of nephrons, are at increased risk of hypertension, impaired kidney function, and cardiovascular disease (6).As the overall mortality of the premature population decreases, the risk of long-term morbidity in this population emerges (7). Barker and Martyn (8) established a framework for th...

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Gudmap

Cited by 240 publications

References 15 publications

Angiotensin II regulates phosphorylation of actin‐associated proteins in human podocytes

Angiotensin II regulates phosphorylation of actin‐associated proteins in human podocytes

Defining cell-type specificity at the transcriptional level in human disease

Evolution of the urinary proteome during human renal development and maturation: variations with gestational and postnatal age

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