Discovery of new glomerular disease-relevant genes by translational profiling of podocytes in vivo

被引：32

作者：

Grgic, Ivica ^{[1
,2
]}

Hofmeister, Andreas F. ^{[1
,2
]}

Genovese, Giulio ^{[3
,4
]}

Bernhardy, Andrea J. ^{[3
]}

Sun, Hua ^{[3
]}

Maarouf, Omar H. ^{[1
]}

Bijol, Vanesa ^{[5
]}

Pollak, Martin R. ^{[3
,4
]}

Humphreys, Benjamin D. ^{[1
,6
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal,Dept Med, Boston, MA 02115 USA

[2] Univ Marburg, Dept Internal Med & Nephrol, Marburg, Germany

[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA 02115 USA

[4] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA

[5] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol & Lab Med, Boston, MA 02115 USA

[6] Harvard Stem Cell Inst, Kidney Grp, Cambridge, MA USA

来源：

KIDNEY INTERNATIONAL | 2014年 / 86卷 / 06期

基金：

美国国家卫生研究院;

关键词：

focal segmental glomerulosclerosis; gene expression; podocyte; proteinuria; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; ANGIOTENSIN-CONVERTING ENZYME; PROTEIN INTERACTION NETWORK; TISSUE GROWTH-FACTOR; CNS CELL-TYPES; DIABETIC-NEPHROPATHY; ACTIN; MICE; EXPRESSION; KIDNEY;

D O I：

10.1038/ki.2014.204

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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 alpha 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 alpha 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.

引用

页码：1116 / 1129

页数：14

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