期刊連結：http://www.gouthyperuricemia.com

Objective: Silent information regulator T1 (SIRT1) plays key roles in the regulation of lipid and glucose homeostasis. In this study, we investigated the potential role of SIRT1 in uric acid (UA) metabolism and explored the possible mechanisms in a human renal proximal tubular cell line (HK-2 cells).
Methods: HK-2 cells were exposed to 500 μM UA to mimic the high-UA condition. The expression levels of urate transport-related proteins, SIRT1, peroxisome proliferator-activated receptor (PPAR)-γ, and PPAR-γ co-activator 1α (PGC-1α) were examined by western blotting. For further research on the mechanisms, SIRT1, PGC-1α and PPAR-γ in HK-2 cells were respectively over-activated by specific agonists or knocked-down by siRNA transfections.
Results: The expression of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were up-regulated while ATP-binding cassette subfamily G 2 (ABCG2) was down-regulated in HK-2 cells under UA stimulation. Resveratrol (RSV), a SIRT1 specific activator, suppressed ABCG2 expression and decreased PGC-1α and PPAR-γ expression. After being activated by agonists, both PGC-1α and PPAR-γ were detected to induce ABCG2 expression. In contrast, blocking SIRT1 promoted the expression of PGC-1α/PPAR-γ and ABCG2, while knocked-down PGC-1α and PPAR-γ decreased the expression of ABCG2.
Conclusion: The present study demonstrates that SIRT1 suppresses ABCG2 expression via PGC-1α/PPAR-γ signaling in HK-2 cells. Based on our in vitro study, SIRT1 amelioration of hyperuricemia might not act through activating UA secretion in the kidney.