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Acute leptin exposure reduces megalin expression and upregulates TGFβ1 in cultured renal proximal tubule cells

Author:
Briffa, Jessica F., Grinfeld, Esther, Mathai, Michael L., Poronnik, Phillip, McAinch, Andrew J., Hryciw, Deanne H.
Source:
Molecular and Cellular Endocrinology 2015 v.401 pp. 25-34
ISSN:
0303-7207
Subject:
AMP-activated protein kinase, Western blotting, albumins, albuminuria, kidney diseases, kidneys, leptin, obesity, opossums, secretion, transforming growth factor beta 1
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.
Agid:
5522800