A human integrin-α3 mutation confers major renal developmental defects.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE54227 | GEO | 2014/12/15
SECONDARY ACCESSION(S): PRJNA236572
REPOSITORIES: GEO
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Project description:Integrin-?3 plays a central role in the interplay of cells, morphogens and ECM, required for proper nephrogenesis, thus adding ITGA3 to the list of CAKUT (congenital anomalies of the kidney and urinary tract)-causing genes. we used renal tissue originally obtained from a patient with an ITGA3 mutation and assessed its gene expression profile as compared to controls
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Project description:We analyzed lncRNAs located in CNV loci associated with congenital anomalies of the kidney and urinary tract (CAKUT). HSALNG0134318 at CNV 22q11 was identified as CAKUT related lncRNA, which was coexpressed with multiple known CAKUT associated genes. To validate our findings, we performed knockdown experiments in HEK293 cell line to characterize the trascriptomic profiles regulated by HSALNG0134318 in human embryonic kidney cells.
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Project description:The objective of the present work was to identify new renal proteins responsible for Congenital Anomalies of the Kidney and of the Urinary Tract (CAKUT pathophysiology). We conducted a comparative LC-MS/MS-based proteomics analysis of amniotic fluids (AF) collected from non-severe CAKUT (ns-CAKUT; n=19), severe CAKUT (s-CAKUT; n=14), and healthy controls (cont; n=22) fetuses. We identified a total of 224 gestational age independent proteins that were significantly different in abundance when comparing (one-way ANOVA corrected p<0.05) the 3 groups of amniotic fluids 2 by 2. We identified 8 gestational-age independent proteins that were in common when comparing the 3 groups two by two, and that were considered as associated to both CAKUT onset and CAKUT severity.
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Project description:Congenital anomalies of the kidneys and urinary tracts (CAKUT) represent the most frequent cause for chronic kidney failure in children. In this dataset, we include the m6A methylated RNA data obtained from children patients with obstructive megaureter (M group) and primary vesicoureteral reflux (V group) . These data are used to obtain a total of 228 mRNAs differ btween these two diseases.
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Project description:Background Congenital anomalies of the kidney and urinary tract (CAKUT) refer to a diverse group of developmental malformations, which are the leading cause of chronic kidney disease and end-stage renal disease in children. The etiology and pathogenesis of CAKUT are complex. In recent years, the relationship between long noncoding RNAs and renal development and disease has attracted much attention. Our previous study established a long noncoding RNA 4933425B07Rik (Rik) overexpression mouse model by inserting the PB transposon and found that overexpression of Rik led to renal hypoplasia. This study aimed to explore the molecular mechanism of renal hypoplasia induced by Rik overexpression in vitro. Results In this study, by constructing Rik overexpression cell models and a Rik knockout cell model to accompany previously developed RikPB/PB;Hoxb7 mice and by applying RNA-seq, RT‒PCR and other experimental methods, it was found that when Rik was highly expressed, the expression of Wnt10b, Fzd8 and β-catenin decreased, while Rik was knock down, the expression of these genes increased. Conclusions The findings suggest that overexpression of Rik leads to renal hypoplasia by inactivating the Wnt/β-catenin signaling pathway. This research perspective may provide a basis for exploring new causes and mechanisms of CAKUT and provide new targets for the prevention and treatment of CAKUT.
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Project description:Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney caused causes ciliary elongation and cystogenesis, and cell-based proximity labelling proteomics and fluorescence microscopy showed alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20 and polycystin-2 (PC2) were are reduced in cilia of DLG1 deficient cells compared to control cells. This phenotype was is recapitulated in vivo and rescuable by re-expression of wildtype DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggested that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.
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Project description:<p>The Genetics of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) contributes data from unrelated individuals who were recruited at the Columbia University Medical Center, NY; the Polish Registry of Congenital Malformations, Poland; the Universities of Parma, Bari and Brescia and the Gaslini Insitute, in Italy; the University of Skopje, Macedonia; and VUMC of Amsterdam, in The Netherlands. These individuals consented to share their data for scientific discovery. The purpose of the study is to investigate the genetic architecture of CAKUT. Genomic DNA samples were genotyped on the Illumina Multi-Ethnic Global Array (MEGA), designed by the MEGA Consortium.</p>
| phs001749 | dbGaP