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10.1038/ki.2014.204

http://scihub22266oqcxt.onion/10.1038/ki.2014.204
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suck abstract from ncbi


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pmid24940801
      Kidney+Int 2014 ; 86 (6 ): 1116-29
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  • Discovery of new glomerular disease-relevant genes by translational profiling of podocytes in vivo #MMPMID24940801
  • Grgic I ; Hofmeister AF ; Genovese G ; Bernhardy AJ ; Sun H ; Maarouf OH ; Bijol V ; Pollak MR ; Humphreys BD
  • Kidney Int 2014[Dec]; 86 (6 ): 1116-29 PMID24940801 show ga
  • Identifying new biomarkers and therapeutic targets for podocytopathies such as focal segmental glomerulosclerosis (FSGS) requires a detailed analysis of transcriptional changes in podocytes over the course of disease. Here we used translating ribosome affinity purification (TRAP) to isolate and profile podocyte-specific mRNA in two different models of FSGS. We expressed enhanced green fluorescent protein-tagged to ribosomal protein L10a in podocytes under the control of the collagen-1?1 promoter, enabling one-step podocyte-specific mRNA isolation over the course of disease. This TRAP protocol robustly enriched known podocyte-specific mRNAs. We crossed Col1?1-eGFP-L10a mice with the Actn4(-/-) and Actn4(+/K256E) models of FSGS and analyzed podocyte transcriptional profiles at 2, 6, and 44 weeks of age. Two upregulated podocyte genes in murine FSGS (CXCL1 and DMPK) were found to be upregulated at the protein level in biopsies from patients with FSGS, validating this approach. There was no dilution of podocyte-specific transcripts during disease. These are the first podocyte-specific RNA expression data sets during aging and in two models of FSGS. This approach identified new podocyte proteins that are upregulated in FSGS and defines novel biomarkers and therapeutic targets for human glomerular disease.
  • |Actinin/*genetics [MESH]
  • |Aging/*genetics/metabolism [MESH]
  • |Animals [MESH]
  • |Biomarkers/metabolism [MESH]
  • |Chemokine CXCL1/genetics/metabolism [MESH]
  • |Collagen Type I, alpha 1 Chain [MESH]
  • |Collagen Type I/genetics [MESH]
  • |Disease Models, Animal [MESH]
  • |Gene Expression Profiling/methods [MESH]
  • |Glomerulosclerosis, Focal Segmental/*genetics/*metabolism [MESH]
  • |Green Fluorescent Proteins/genetics [MESH]
  • |Humans [MESH]
  • |Mice [MESH]
  • |Mice, Knockout [MESH]
  • |Myotonin-Protein Kinase/genetics/metabolism [MESH]
  • |Neoplasm Proteins [MESH]
  • |Oligonucleotide Array Sequence Analysis [MESH]
  • |Podocytes/*metabolism [MESH]
  • |Protein Biosynthesis [MESH]
  • |RNA, Messenger/*analysis [MESH]
  • |Ribosomal Protein L10 [MESH]
  • |Ribosomal Proteins/genetics [MESH]


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