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dc.contributor.authorBriffa, Jessica F
dc.contributor.authorGrinfeld, Esther
dc.contributor.authorMathai, Michael L
dc.contributor.authorPoronnik, Phillip
dc.contributor.authorMcAinch, Andrew J
dc.contributor.authorHryciw, Deanne H
dc.date.accessioned2017-07-17T05:00:14Z
dc.date.available2017-07-17T05:00:14Z
dc.date.issued2015
dc.identifier.issn0303-7207
dc.identifier.doi10.1016/j.mce.2014.11.024
dc.identifier.urihttp://hdl.handle.net/10072/341912
dc.description.abstractIncreased leptin concentrations observed in obesity can lead to proteinuria, suggesting that leptin may play a role in obesity-related kidney disease. Obesity reduces activation of AMP-activated protein kinase (AMPK) and increases transforming growth factor-β1 (TGF-β1) expression in the kidney, leading to albuminuria. Thus we investigated if elevated leptin altered AMPK and TGF-β1 signaling in proximal tubule cells (PTCs). In opossum kidney (OK) PTCs Western blot analysis demonstrated that leptin upregulates TGF-β1 secretion (0.50 µg/ml) and phosphorylated AMPKα (at 0.25, and 0.50 µg/ml), and downregulates megalin expression at all concentrations (0.05–0.50 µg/ml). Using the AMPK inhibitor, Compound C, leptin exposure regulated TGF-β1 expression and secretion in PTCs via an AMPK mediated pathway. In addition, elevated leptin exposure (0.50 µg/ml) reduced albumin handling in OK cells independently of megalin expression. This study demonstrates that leptin upregulates TGF-β1, reduces megalin, and reduces albumin handling in PTCs by an AMPK mediated pathway.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom25
dc.relation.ispartofpageto34
dc.relation.ispartofjournalMolecular and Cellular Endocrinology
dc.relation.ispartofvolume401
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchAgricultural, veterinary and food sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchMedical physiology not elsewhere classified
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode30
dc.subject.fieldofresearchcode32
dc.subject.fieldofresearchcode320899
dc.titleAcute leptin exposure reduces megalin expression and upregulates TGFB1 in cultured renal proximal tubule cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorSkelly, Deanne


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