Acute leptin exposure reduces megalin expression and upregulates TGF beta 1 in cultured renal proximal tubule cells

作者：Briffa Jessica F; Grinfeld Esther; Mathai Michael L; Poronnik Phillip; McAinch Andrew J; Hryciw Deanne H^*

来源：Molecular and Cellular Endocrinology, 2015, 401(C): 25-34.

DOI：10.1016/j.mce.2014.11.024

• Leptin
• Megalin
• Proximal tubule
• TGF-beta 1
• AMPK

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-beta 1 (TGF-beta 1) expression in the kidney, leading to albuminuria. Thus we investigated if elevated leptin altered AMPK and TGF-beta 1 signaling in proximal tubule cells (PTCs). In opossum kidney (OK) PTCs Western blot analysis demonstrated that leptin upregulates TGF-beta 1 secretion (0.50 mu g/ml) and phosphorylated AMPK alpha (at 0.25, and 0.50 mu g/ml), and downregulates megalin expression at all concentrations (0.05-0.50 mu g/ml). Using the AMPK inhibitor, Compound C, leptin exposure regulated TGF-beta 1 expression and secretion in PTCs via an AMPK mediated pathway. In addition, elevated leptin exposure (0.50 mu g/ml) reduced albumin handling in OK cells independently of megalin expression. This study demonstrates that leptin upregulates TGF-beta 1, reduces megalin, and reduces albumin handling in PTCs by an AMPK mediated pathway.

• 出版日期2015-2-5