Genomics

Dataset Information

0

Gene Expression Profiling of Glomeruli from a mouse model of Denys-Drash Syndrome


ABSTRACT: The Wilms tumor-suppressor gene WT1, a key player in renal development, also has a crucial role in maintenance of the glomerulus in the mature kidney. However, molecular pathways orchestrated by WT1 in podocytes, where it is highly expressed, remain unknown. Their defects are thought to modify the cross-talk between podocytes and other glomerular cells and ultimately lead to glomerular sclerosis, as observed in diffuse mesangial sclerosis (DMS) a nephropathy associated with WT1 mutations. To identify podocyte WT1 targets, we generated a novel DMS mouse line, performed gene expression profiling in isolated glomeruli, and identified excellent candidates that may modify podocyte differentiation and growth factor signalling in glomeruli. Scel, encoding sciellin, a protein of the cornified envelope in the skin, and sulf1, encoding a 6-O endosulfatase, are shown to be expressed in wild type podocytes and to be strongly down-regulated in mutants. Co-expression of Wt1, Scel and Sulf1 was also found in a mesonephric cell line, and siRNA-mediated knockdown of WT1 decreased Scel and Sulf1 mRNAs and proteins. By ChIP we show that Scel and Sulf1 are direct WT1 targets. Cyp26a1, encoding an enzyme involved in the degradation of retinoic acid, is shown to be up-regulated in mutant podocytes. Cyp26a1 may play a role in the development of glomerular lesions but does not seem to be regulated by WT1. These results provide novel clues in our understanding of normal glomerular function and early events involved in glomerulosclerosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE18358 | GEO | 2009/10/02

SECONDARY ACCESSION(S): PRJNA118113

REPOSITORIES: GEO

Similar Datasets

| E-GEOD-18358 | biostudies-arrayexpress
| E-GEOD-64063 | biostudies-arrayexpress
| E-GEOD-51834 | biostudies-arrayexpress
2014-12-11 | GSE64063 | GEO
2017-07-31 | GSE89263 | GEO
2021-12-23 | GSE186547 | GEO
2018-12-04 | GSE99583 | GEO
2023-11-01 | GSE213174 | GEO
2014-10-14 | GSE51834 | GEO
2022-10-25 | GSE216088 | GEO