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Increased Wnt and Notch signaling: A clue to the renal disease in Schimke immuno-osseous dysplasia? [array]

ABSTRACT: Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in SWI/SNF-related matrix associated actin-dependent regulator of chromatin, subfamily A-like protein 1 (SMARCAL1). Changes in gene expression appear to underlie the immunodeficiency and arteriosclerosis of SIOD; therefore, we hypothesized that SMARCAL1 deficiency alters renal gene expression to cause the focal segmental glomerulosclerosis (FSGS) of SIOD, and that these gene expression alterations would be comparable to those observed in isolated FSGS. We tested this hypothesis by gene expression microarray analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE81156 | GEO | 2016/10/31

SECONDARY ACCESSION(S): PRJNA320766

REPOSITORIES: GEO

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Increased Wnt and Notch signaling: A clue to the renal disease in Schimke immuno-osseous dysplasia? [RNA-Seq]

Project description:Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in SWI/SNF-related matrix associated actin-dependent regulator of chromatin, subfamily A-like protein 1 (SMARCAL1). Changes in gene expression appear to underlie the immunodeficiency and arteriosclerosis of SIOD; therefore, we hypothesized that SMARCAL1 deficiency alters renal gene expression to cause the focal segmental glomerulosclerosis (FSGS) of SIOD. We tested this hypothesis by transcriptome analysis and quantitative reverse transcription PCR (qRT-PCR) of an SIOD patient kidney, a genetic screen and immunofluorescence. These showed increased expression of genes in the Wnt and Notch signaling pathways in an SIOD patient kidney, interaction of Marcal1 with genes encoding components of the Wnt and Notch signaling pathways, and increased levels of unphosphorylated b-catenin and Notch1 intracellular domain (NICD) in the glomeruli of SIOD patient kidneys. Given that increased Wnt and Notch activity are established causes of FSGS, we hypothesize that SMARCAL1 deficiency increases the activity of one or both of these pathways to cause the renal disease of most SIOD patients.

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Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression (1)

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SMARCAL1 modulates cellular triglyceride storage and expenditure in response to cell growth states via interaction with ANGPTL3 (RNA-Seq 2)

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