dc.contributor.author | Briffa, Jessica F | |
dc.contributor.author | Grinfeld, Esther | |
dc.contributor.author | Mathai, Michael L | |
dc.contributor.author | Poronnik, Phillip | |
dc.contributor.author | McAinch, Andrew J | |
dc.contributor.author | Hryciw, Deanne H | |
dc.date.accessioned | 2017-07-17T05:00:14Z | |
dc.date.available | 2017-07-17T05:00:14Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 0303-7207 | |
dc.identifier.doi | 10.1016/j.mce.2014.11.024 | |
dc.identifier.uri | http://hdl.handle.net/10072/341912 | |
dc.description.abstract | Increased 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.relation.ispartofpagefrom | 25 | |
dc.relation.ispartofpageto | 34 | |
dc.relation.ispartofjournal | Molecular and Cellular Endocrinology | |
dc.relation.ispartofvolume | 401 | |
dc.subject.fieldofresearch | Biological sciences | |
dc.subject.fieldofresearch | Agricultural, veterinary and food sciences | |
dc.subject.fieldofresearch | Biomedical and clinical sciences | |
dc.subject.fieldofresearch | Medical physiology not elsewhere classified | |
dc.subject.fieldofresearchcode | 31 | |
dc.subject.fieldofresearchcode | 30 | |
dc.subject.fieldofresearchcode | 32 | |
dc.subject.fieldofresearchcode | 320899 | |
dc.title | Acute leptin exposure reduces megalin expression and upregulates TGFB1 in cultured renal proximal tubule cells | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Skelly, Deanne | |