Acute leptin exposure reduces megalin expression and upregulates TGF beta 1 in cultured renal proximal tubule cells
AuthorBriffa, JF; Grinfeld, E; Mathai, ML; Poronnik, P; McAinch, AJ; Hryciw, DH
Source TitleMolecular and Cellular Endocrinology
Document TypeJournal Article
CitationsBriffa, J. F., Grinfeld, E., Mathai, M. L., Poronnik, P., McAinch, A. J. & Hryciw, D. H. (2015). Acute leptin exposure reduces megalin expression and upregulates TGF beta 1 in cultured renal proximal tubule cells. Molecular and Cellular Endocrinology, 401 (C), pp.25-34. https://doi.org/10.1016/j.mce.2014.11.024.
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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.
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