TY  - JOUR
AU  - Briffa, JF
AU  - Grinfeld, E
AU  - Mathai, ML
AU  - Poronnik, P
AU  - McAinch, AJ
AU  - Hryciw, DH
Y2  - 2020/05/22
Y1  - 2015/02/05
SN  - 0303-7207
UR  - http://hdl.handle.net/11343/239178
AB  - 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.
LA  - English
PB  - Elsevier
T1  - Acute leptin exposure reduces megalin expression and upregulates TGF beta 1 in cultured renal proximal tubule cells
DO  - 10.1016/j.mce.2014.11.024
IS  - Molecular and Cellular Endocrinology
VL  - 401
IS  - C
SP  - 25-34
ER  -