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Träfflista för sökning "WFRF:(Takemoto Minoru) srt2:(2005-2009)"

Sökning: WFRF:(Takemoto Minoru) > (2005-2009)

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1.
  • Bondjers, Cecilia, 1974, et al. (författare)
  • Microarray analysis of blood microvessels from PDGF-B and PDGF-Rbeta mutant mice identifies novel markers for brain pericytes.
  • 2006
  • Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 20:10, s. 1703-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Normal blood microvessels are lined by pericytes, which contribute to microvessel development and stability through mechanisms that are poorly understood. Pericyte deficiency has been implicated in the pathogenesis of microvascular abnormalities associated with diabetes and tumors. However, the unambiguous identification of pericytes is still a problem because of cellular heterogeneity and few available molecular markers. Here we describe an approach to identify pericyte markers based on transcription profiling of pericyte-deficient brain microvessels isolated from platelet-derived growth factor (PDGF-B)-/- and PDGF beta receptor (PDGFRbeta)-/- mouse mutants. The approach was validated by the identification of known pericyte markers among the most down-regulated genes in PDGF-B-/- and PDGFRbeta-/- microvessels. Of candidates for novel pericyte markers, we selected ATP-sensitive potassium-channel Kir6.1 (also known as Kcnj8) and sulfonylurea receptor 2, (SUR2, also known as Abcc9), both part of the same channel complex, as well as delta homologue 1 (DLK1) for in situ hybridization, which demonstrated their specific expression in brain pericytes of mouse embryos. We also show that Kir6.1 is highly expressed in pericytes in brain but undetectable in pericytes in skin and heart. The three new brain pericyte markers are signaling molecules implicated in ion transport and intercellular signaling, potentially opening new windows on pericyte function in brain microvessels.
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2.
  • He, L, et al. (författare)
  • Glomerulus-specific mRNA transcripts and proteins identified through kidney expressed sequence tag database analysis
  • 2007
  • Ingår i: Kidney International. - 1523-1755 .- 0085-2538. ; 71:9, s. 889-900
  • Tidskriftsartikel (refereegranskat)abstract
    • The kidney glomerulus plays a crucial role in blood filtration but the molecular composition and physiology of the glomerulus is not well understood. We previously constructed and large-scale sequenced four mouse glomerular expressed sequence tag (EST) libraries from newborn and adult mouse glomeruli. Here, we compared glomerular EST profiles with whole kidney EST profiles, thereby identifying 497 transcripts corresponding to UniGene clusters that were glomerulus-enriched, that is expressed more abundantly in glomeruli than in whole kidney. These include several known protein-coding glomerulus-specific transcripts critical for glomerulus development and function, but also a large number of gene transcripts, which have not previously been shown to be expressed in the glomerulus, or implicated in glomerular functions. We used in situ hybridization to demonstrate glomerulus-specific RNA expression for six novel glomerular genes and the public Human Protein Atlas to verify glomerular protein expression for another two. The higher mRNA abundance for the eight genes in glomeruli compared with whole kidney was also verified by Taqman quantitative polymerase chain reaction. We surmise that the further characterization of these genes and proteins will increase our understanding of glomerular development and physiology.
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3.
  • He, Liqun, et al. (författare)
  • The glomerular transcriptome and a predicted protein-protein interaction network
  • 2008
  • Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 19:2, s. 260-268
  • Tidskriftsartikel (refereegranskat)abstract
    • To increase our understanding of the molecular composition of the kidney glomerulus, we performed a meta-analysis of available glomerular transcriptional profiles made from mouse and man using five different methodologies. We generated a combined catalogue of glomerulus-enriched genes that emerged from these different sources and then used this to construct a predicted protein-protein interaction network in the glomerulus (GlomNet). The combined glomerulus-enriched gene catalogue provides the most comprehensive picture of the molecular composition of the glomerulus currently available, and GlomNet contributes an integrative systems biology approach to the understanding of glomerular signaling networks that operate during development, function, and disease.
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4.
  • Patrakka, Jaakko, et al. (författare)
  • Expression and subcellular distribution of novel glomerulus-associated proteins dendrin, ehd3, sh2d4a, plekhh2, and 2310066E14Rik
  • 2007
  • Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 18:3, s. 689-697
  • Tidskriftsartikel (refereegranskat)abstract
    • The glomerular capillary tuft is a highly specialized microcapillary that is dedicated to function as a sophisticated molecular sieve. The glomerulus filter has a unique molecular composition, and several essential glomerular proteins are expressed in the kidney exclusively by glomerular podocytes. A catalog of > 300 glomerulus-upregulated transcripts that were identified using expressed sequence tag profiling and microarray analysis was published recently. This study characterized the expression profile of five glomerulus-upregulated transcripts/proteins (ehd3, dendrin, sh2d4a, plekhh2, and 2310066E14Rik) in detail. The expression pattern of these novel glomerular transcripts in various mouse tissues was studied using reverse transcriptase-PCR, Northern blotting, and in situ hybridization. For studying the distribution of corresponding proteins, polyclonal antibodies were raised against the gene products, and Western blotting, immunofluorescence, and immunoelectron microscopic analyses were performed. Remarkably, it was discovered that all five transcripts/proteins were expressed in the kidney exclusively by glomerular cells. Ehd3 was expressed only by glomerular endothelial cells. Importantly, ehd3 is the first gene ever shown to be expressed exclusively by glomerular endothelial cells and not by other endothelial cells in the kidney. Dendrin, sh2d4a, plekhh2, and 2310066E14Rik, however, were transcribed solely by podocytes. With the use of polyclonal antibodies, dendrin, sh2d4a, and plekhh2 proteins were localized to the slit diaphragm and the foot process, whereas 2310066E14Rik protein was localized to the podocyte major processes and cell body. This study provides fresh insights into glomerular biology and uncovers new possibilities to explore the role of these novel proteins in the glomerular physiology and pathology.
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5.
  • Sun, Ying, et al. (författare)
  • Glomerular Transcriptome Changes Associated with Lipopolysaccharide-Induced Proteinuria
  • 2009
  • Ingår i: American Journal of Nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 29:6, s. 558-570
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Global gene expression patterns have recently been characterized in normal glomeruli, but gene expression changes that accompany glomerular disease remain poorly characterized. Method: Here, we mapped global glomerular gene expression profile changes occurring in conjunction with lipopolysaccharide (LPS)-induced proteinuria in mice. Results: We observed dramatic transcriptional reprogramming in glomeruli in response to LPS, representing some 20% of all genes and about 45% of the genes that are normally highly expressed in glomeruli. Bioinformatic analysis revealed significant changes in transcripts encoding proteins involved in the regulation of adherence junctions, actin cytoskeleton and survival in podocytes. In the LPS-treated mice, we observed dysregulation of genes expressed in glomerular endothelial and mesangial cells and in podocytes, there was also a significant decrease in podocyte number. Moreover, collagen alpha 1, alpha 2 (IV) and laminin 10 (laminin alpha 5 beta 1 gamma 1), which are expressed in immature glomeruli, were upregulated in the glomeruli of LPS-treated mice, suggesting remodeling of the glomerular basement membrane and activation of mesangial cells. By superimposing the LPS-induced changes onto GlomNet, a protein-protein interaction network was predicted for podocyte proteins affected by LPS. Conclusions: The detected changes in glomerular gene expression and their involvement in protein interaction networks provide putative markers for early and transient glomerular injury and proteinuria. Copyright (c) 2009 S. Karger AG, Basel
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6.
  • Takemoto, Minoru, et al. (författare)
  • Large-scale identification of genes implicated in kidney glomerulus development and function.
  • 2006
  • Ingår i: The EMBO journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 25:5, s. 1160-74
  • Tidskriftsartikel (refereegranskat)abstract
    • To advance our understanding of development, function and diseases in the kidney glomerulus, we have established and large-scale sequenced cDNA libraries from mouse glomeruli at different stages of development, resulting in a catalogue of 6053 different genes. The glomerular cDNA clones were arrayed and hybridized against a series of labeled targets from isolated glomeruli, non-glomerular kidney tissue, FACS-sorted podocytes and brain capillaries, which identified over 300 glomerular cell-enriched transcripts, some of which were further sublocalized to podocytes, mesangial cells and juxtaglomerular cells by in situ hybridization. For the earliest podocyte marker identified, Foxc2, knockout mice were used to analyze the role of this protein during glomerular development. We show that Foxc2 controls the expression of a distinct set of podocyte genes involved in podocyte differentiation and glomerular basement membrane maturation. The primary podocyte defects also cause abnormal differentiation and organization of the glomerular vascular cells. We surmise that studies on the other novel glomerulus-enriched transcripts identified in this study will provide new insight into glomerular development and pathomechanisms of disease.
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