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Comparative protein profiling of wild type and ILDR2 knockout podocytes

ABSTRACT: The role of ILDR2 in podocytes, specialized epithelial cells in the kidney, is still unknown. We investigated the role of ILDR2 in glomeruli and its influence on blood filtration. Ildr2 knockout mice exhibited glomerular hypertrophy and decreased podocyte density, however, did not develop effacement of podocyte foot processes or proteinuria. LC-MS/MS proteomic analysis of isolated glomeruli showed an increase in matrix proteins such as fibronectin and agrin. This suggests a protective role of ILDR2 in glomerulopathies.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Glomerular Visceral Epithelial Cell

SUBMITTER: Elke Hammer

LAB HEAD: Elke Hammer

PROVIDER: PXD056696 | Pride | 2024-11-13

REPOSITORIES: Pride

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			Action	DRS
	20210419_Exp_AW_Anat_14_111_WT_0d.raw	Raw
	20210419_Exp_AW_Anat_15_115_KO_0d.raw	Raw
	20210419_Exp_AW_Anat_17_68_WT_0d.raw	Raw
	20210419_Exp_AW_Anat_18_71_WT_0d.raw	Raw
	20210419_Exp_AW_Anat_20_113_KO_0d.raw	Raw

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Genome-wide analysis of WT1-controlled gene expression in podocytes

Project description:We identified binding sites of the Wilms' tumor suppressor protein WT1 in the mouse podocyte genome in vivo by ChIP-seq. Furthermore, we provide a podocyte transcriptome derived from primary podocytes that were isolated by FACS on mouse glomeruli. In short, we show that WT1 activates a highly specific podocyte transcriptome by binding to putative podocyte-specific enhancers and TSS of target genes. Genes bound by WT1 in podocytes include the majority of genes mutated in hereditary podocytopathies as well as components of the slit diaphragm, actin cytoskeleton, extracellular matrix, and within endocytosis pathways. Furthermore, we infer a podocyte TF network from DNA-binding motifs enriched at WT1-bound loci that includes Tead, Lmx1b, Mafb, Tcf21, and Fox-class transcription factors. Examination of transcription factor binding sites for WT1 by ChIP-seq. Transcriptome analysis of podocytes by RNA-seq.

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Comparative protein profiling of wild type and zyxin knockout podocytes

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Project description:Calcimimetic agents allosterically increase the calcium (Ca2+) sensitivity of the calcium-sensing receptor (CaSR), which is expressed in the tubular system and to a lesser extent in podocytes. Activation of this receptor can reduce glomerular proteinuria and structural damage in proteinuric animal models. However, the precise role of the podocyte CaSR is still unclear. A CaSR knockdown in cultured murine podocytes and a podocyte-specific CaSR knockout in BALB/c mice were generated to study its role in proteinuria and kidney function. Podocyte CaSR knockdown abolished the calcimimetic R-568 mediated Ca2+-influx, disrupted the actin cytoskeleton, reduced cellular attachment and migration velocity. Adriamycin (ADR)-induced proteinuria enhanced glomerular CaSR expression in wild type mice. Albuminuria, podocyte foot process effacement, podocyte loss and glomerular sclerosis were significantly more pronounced in ADR-treated podocyte-specific CaSR knockout mice compared to wild type littermates. The co-treatment of WT mice with ADR and the calcimimetic cinacalcet reduced the proteinuria in WT, but not in podocyte specific CaSR knockout mice. In addition, four children with nephrotic syndrome, objecting glucocorticoid therapy, were treated with cinacalcet for 1 to 33 days. Proteinuria declined transiently by up to 96% and edema resolved. The activation of podocyte CaSR regulates key podocyte functions in vitro and reduces toxin induced proteinuria and glomerular damage in mice. Our findings suggest a potential novel role of CaSR signaling in control of glomerular disease. Proteomic samples: two backgrounds (CaSR Knockdown vs WT) two conditions (Treatment = 1µM R568 vs untreated control) two timepoints (24h and 48h) five replicates each 2 x 2 x 2 x 5 = 40 samples

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Comparison of Glomerular and Podocyte mRNA Profiles in eNOS-/- Diabetic Mice Induced by Streptozotocin

Project description:We compared mRNA profiles of isolated glomeruli versus sorted podocytes between diabetic and control mice. IRG mice crossed with eNOS-/- mice were further bred with podocin-rTTA and TetON-Cre mice to permanently label podocytes before the diabetic injury. Diabetes was induced by injection of streptozotocin. mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice at 10 weeks after induction of diabetes were examined. Consistent with the previous reports, expression of podocyte-specific markers in the glomeruli were down-regulated in the diabetic mice compared to controls. However, these differences disappeared when mRNA levels were corrected for podocyte number per glomerulus. Interestingly, the expression of these markers was not altered in sorted podocytes from diabetic mice, suggesting that the reduced expression of podocyte markers in isolated glomeruli is likely a secondary effect of reduced podocyte number, rather than the loss of differentiation markers. Analysis of the differentially expressed genes in diabetic mice also revealed distinct up-regulated pathways in the glomeruli (mitochondrial function and oxidative stress) and podocytes (actin organization). In conclusion, our data suggest that podocyte-specific gene expression in transcriptome obtained from the whole glomeruli may not represent those of podocytes in the diabetic kidney. We compared mRNA profiles of isolated glomeruli versus sorted podocytes between diabetic and control mice.

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