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  • Acute leptin exposure reduces megalin expression and upregulates TGFB1 in cultured renal proximal tubule cells

    Author(s)
    Briffa, Jessica F
    Grinfeld, Esther
    Mathai, Michael L
    Poronnik, Phillip
    McAinch, Andrew J
    Hryciw, Deanne H
    Griffith University Author(s)
    Skelly, Deanne
    Year published
    2015
    Metadata
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    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 ...
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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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    Journal Title
    Molecular and Cellular Endocrinology
    Volume
    401
    DOI
    https://doi.org/10.1016/j.mce.2014.11.024
    Subject
    Biological sciences
    Agricultural, veterinary and food sciences
    Biomedical and clinical sciences
    Medical physiology not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/341912
    Collection
    • Journal articles

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