Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA121863 | ENA |
REPOSITORIES: ENA
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Project description:The endocytic receptor megalin constitutes the main pathway for clearance of plasma proteins from the glomerular filtrate in the proximal tubules. However, little is know about the mechanisms that control receptor activity. A widely discussed hypothesis states that the intracellular domain (ICD) of megalin, released upon ligand binding, acts as a transcription regulator to suppress receptor expression - a mechanism proposed to safeguard the proximal tubules from protein overload. Here, we have put this hypothesis to the test by generating a mouse model co-expressing the soluble ICD and the full-length receptor. Despite pronounced expression in the proximal tubules, the ICD failed to exert any effects on renal proximal tubular function such as megalin expression, protein retrieval, or renal gene transcription. Thus, our data argue that the ICD does not play a role in regulation of megalin activity in vivo in the proximal tubules. We used microarrays to compare gene expression profile in adult kidney from a new mouse model expressing the intracellular domain of megalin with wildtype. 10 week old mice were collected for RNA extraction and hybridization on Affymetrix microarrays. Three individuals for each genotype were analyzed comparing heterozygous animals for the intracellular domain of megalin with littermates controls.
2011-01-01 | E-GEOD-19778 | biostudies-arrayexpress
Project description:The endocytic receptor megalin constitutes the main pathway for clearance of plasma proteins from the glomerular filtrate in the proximal tubules. However, little is know about the mechanisms that control receptor activity. A widely discussed hypothesis states that the intracellular domain (ICD) of megalin, released upon ligand binding, acts as a transcription regulator to suppress receptor expression - a mechanism proposed to safeguard the proximal tubules from protein overload. Here, we have put this hypothesis to the test by generating a mouse model co-expressing the soluble ICD and the full-length receptor. Despite pronounced expression in the proximal tubules, the ICD failed to exert any effects on renal proximal tubular function such as megalin expression, protein retrieval, or renal gene transcription. Thus, our data argue that the ICD does not play a role in regulation of megalin activity in vivo in the proximal tubules. We used microarrays to compare gene expression profile in adult kidney from a new mouse model expressing the intracellular domain of megalin with wildtype.
2011-01-01 | GSE19778 | GEO
Project description:Diabetic kidney disease is a major complication in diabetes mellitus, and the most common reason for end-stage renal disease. Patients suffering from diabetes mellitus encounter glomerular damage by basement membrane thickening, and develop albuminuria. Subsequently, albuminuria can deteriorate the tubular function and impair the renal outcome. The impact of diabetic stress conditions on the metabolome was investigated by untargeted gas chromatography-mass spectrometry (GC-MS) analyses. The results were validated by qPCR analyses. In total, four cell lines were tested, representing the glomerulus, proximal nephron tubule, and collecting duct. Both murine and human cell lines were used. In podocytes, proximal tubular and collecting duct cells, high glucose concentrations led to global metabolic alterations in amino acid metabolism and the polyol pathway. Albumin overload led to the further activation of the latter pathway in human proximal tubular cells. In the proximal tubular cells, aldo-keto reductase was concordantly increased by glucose, and partially increased by albumin overload. Here, the combinatorial impact of two stressful agents in diabetes on the metabolome of kidney cells was investigated, revealing effects of glucose and albumin on polyol metabolism in human proximal tubular cells. This study shows the importance of including highly concentrated albumin in in vitro studies for mimicking diabetic kidney disease.
2019-10-08 | MTBLS1093 | MetaboLights
Project description:Kidney damage involves the progressive and inexorable destruction of tubular and glomerular system. However, it is known that the patients survive AKI often recover renal structure and function. Correspondingly, previous studies demonstrated tubular regeneration in mice after massive kidney injury and linked mouse Sox9+ renal progenitor cells to this process. Here we show that renal progenitor cells can be cloned from renal needle biopsy sample of CKD patients. Progenitor cells can readily assembly into “kidney organoids” expressing proximal/distal tubular cell markers in 3D culture.
2022-04-22 | GSE119426 | GEO
Project description:Shiga toxin type 2 (Stx2) from Escherichia coli is thought to be a main factor to casue renal dysfunction in Enterohemorrhagic E. coli (EHEC) infection. The renal dysfunction caused by the proximal tubular defects can be detected in the earlier EHEC infection. However, the precise information of gene expression from proximal tubular epithelial cells has yet to be clarified. We performed microarray experiments using Stx2-injected mouse kidney and Stx2-treated human renal proximal tubular epithelial cells (RPTEC), and extracted common genes that were differentially expressed.
2022-01-01 | GSE172466 | GEO
Project description:Shiga toxin type 2 (Stx2) from Escherichia coli is thought to be a main factor to casue renal dysfunction in Enterohemorrhagic E. coli (EHEC) infection. The renal dysfunction caused by the proximal tubular defects can be detected in the earlier EHEC infection. However, the precise information of gene expression from proximal tubular epithelial cells has yet to be clarified. We performed microarray experiments using Stx2-injected mouse kidney and Stx2-treated human renal proximal tubular epithelial cells (RPTEC), and extracted common genes that were differentially expressed.
2022-01-01 | GSE172465 | GEO
Project description:In order to identify the effects of OCRL depletion on the proximal tubular renal cells transcriptome, we performed Affymetrix Gene-Chip hybridization experiments Transcriptome analysis of the proximal tubular cells depleted of OCRL
2016-12-20 | GSE54284 | GEO
Project description:Kidney damage involves the progressive and inexorable destruction of tubular and glomerular system. However, it is known that the patients survive AKI often recover renal structure and function. Correspondingly, previous studies demonstrated tubular regeneration in mice after massive kidney injury and linked mouse Sox9+ renal progenitor cells to this process. Here we show that progenitor cells can be cloned from mouse medulla and cortex. Clones can be grown from a single cell and indefinitely passaged. Progenitor cells derived from renal medulla can readily assembly into “kidney organoids” expressing proximal/distal tubular cell markers in 3D culture.
2022-04-22 | GSE120049 | GEO
Project description:Effect of 4.2 micromolar Cyclosporine A on human renal proximal tubular cell line HK-2 over 48 hours
2008-06-11 | E-GEOD-1403 | biostudies-arrayexpress
Project description:This experiment is designed to investigate common transcriptional alterations in renal proximal tubular cell cultures due to nephrotoxin exposure.
2011-02-01 | E-MEXP-2599 | biostudies-arrayexpress