{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Korstanje R"],"funding":["NIA NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["3271-3277"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5084883"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(11)"],"pubmed_abstract":["Changes in metabolite levels of the kynurenine pathway have been observed in patients with CKD, suggesting involvement of this pathway in disease pathogenesis. Our recent genetic analysis in the mouse identified the kynurenine 3-mono-oxygenase (KMO) gene (Kmo) as a candidate gene associated with albuminuria. This study investigated this association in more detail. We compared KMO abundance in the glomeruli of mice and humans under normal and diabetic conditions, observing a decrease in glomerular KMO expression with diabetes. Knockdown of kmo expression in zebrafish and genetic deletion of Kmo in mice each led to a proteinuria phenotype. We observed pronounced podocyte foot process effacement on long stretches of the filtration barrier in the zebrafish knockdown model and mild podocyte foot process effacement in the mouse model, whereas all other structures within the kidney remained unremarkable. These data establish the candidacy of KMO as a causal factor for changes in the kidney leading to proteinuria and indicate a functional role for KMO and metabolites of the tryptophan pathway in podocytes."],"journal":["Journal of the American Society of Nephrology : JASN"],"pubmed_title":["Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria."],"pmcid":["PMC5084883"],"funding_grant_id":["P20 GM104318","P30 AG038070","P20 GM103423","P30 CA034196","P50 GM076468"],"pubmed_authors":["Deutsch K","Schiffer M","Roberts IS","Sheehan S","Haller H","Bolanos-Palmieri P","Brasen JH","Korstanje R","Staggs L","Hanke N","Schroder P","Savage H"],"additional_accession":[]},"is_claimable":false,"name":"Loss of Kynurenine 3-Mono-oxygenase Causes Proteinuria.","description":"Changes in metabolite levels of the kynurenine pathway have been observed in patients with CKD, suggesting involvement of this pathway in disease pathogenesis. Our recent genetic analysis in the mouse identified the kynurenine 3-mono-oxygenase (KMO) gene (Kmo) as a candidate gene associated with albuminuria. This study investigated this association in more detail. We compared KMO abundance in the glomeruli of mice and humans under normal and diabetic conditions, observing a decrease in glomerular KMO expression with diabetes. Knockdown of kmo expression in zebrafish and genetic deletion of Kmo in mice each led to a proteinuria phenotype. We observed pronounced podocyte foot process effacement on long stretches of the filtration barrier in the zebrafish knockdown model and mild podocyte foot process effacement in the mouse model, whereas all other structures within the kidney remained unremarkable. These data establish the candidacy of KMO as a causal factor for changes in the kidney leading to proteinuria and indicate a functional role for KMO and metabolites of the tryptophan pathway in podocytes.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Nov","modification":"2025-04-18T20:51:30.292Z","creation":"2019-03-27T02:27:46Z"},"accession":"S-EPMC5084883","cross_references":{"pubmed":["27020856"],"doi":["10.1681/ASN.2015070835","10.1681/asn.2015070835"]}}