Journal article
Discovery of new glomerular disease–relevant genes by translational profiling of podocytes in vivo
Kidney international, Vol.86(6), pp.1116-1129
12/01/2014
DOI: 10.1038/ki.2014.204
PMCID: PMC4245460
PMID: 24940801
Abstract
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-1α1 promoter, enabling one-step podocyte-specific mRNA isolation over the course of disease. This TRAP protocol robustly enriched known podocyte-specific mRNAs. We crossed Col1α1-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.
Details
- Title: Subtitle
- Discovery of new glomerular disease–relevant genes by translational profiling of podocytes in vivo
- Creators
- Ivica Grgic - Philipps University of MarburgAndreas F. Hofmeister - Philipps University of MarburgGiulio Genovese - Beth Israel Deaconess Medical CenterAndrea J. Bernhardy - Beth Israel Deaconess Medical CenterHua Sun - Beth Israel Deaconess Medical CenterOmar H. Maarouf - Brigham and Women's HospitalVanesa Bijol - Brigham and Women's HospitalMartin R. Pollak - Beth Israel Deaconess Medical CenterBenjamin D. Humphreys - Harvard Stem Cell Institute
- Resource Type
- Journal article
- Publication Details
- Kidney international, Vol.86(6), pp.1116-1129
- Publisher
- Elsevier Inc
- DOI
- 10.1038/ki.2014.204
- PMID
- 24940801
- PMCID
- PMC4245460
- ISSN
- 0085-2538
- eISSN
- 1523-1755
- Language
- English
- Date published
- 12/01/2014
- Academic Unit
- Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics
- Record Identifier
- 9984384313402771
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