Metabolic reprogramming is a driver of autosomal dominant polycystic kidney disease (ADPKD) progression and a potential therapeutic intervention route. We showed before that the AMP-associated protein kinase (AMPK) activator salsalate attenuates cystic disease progression. Here, we aim to study the early, direct effects of short salsalate treatment in adult-onset conditional deletion mice. Cystic mice were treated with salsalate for two weeks, after which NMR metabolomics and RNA sequencing analyses were performed. deletion resulted in clear metabolomic dysregulation. Short salsalate treatment has small, but significant, effects, reverting acetylcarnitine and phosphocholine concentrations back to wildtype levels, and showing associations with altered purine metabolism. RNA sequencing revealed that short salsalate treatment, next to restoring energy metabolism toward wildtype levels, also affects cell proliferation and inflammation, in PKD. We show that salsalate positively affects major dysregulated processes in ADPKD: energy metabolism, cell proliferation, and inflammation, providing more insights into its working mechanisms.

中文翻译：

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短期水杨酸给药影响多囊肾病的细胞增殖、代谢和炎症


代谢重编程是常染色体显性多囊肾病 (ADPKD) 进展的驱动因素，也是潜在的治疗干预途径。我们之前表明，AMP 相关蛋白激酶 (AMPK) 激活剂双水杨酸可减轻囊性疾病的进展。在这里，我们的目标是研究短水杨酸治疗对成年发病条件缺失小鼠的早期直接影响。囊性小鼠接受双水杨酸治疗两周，然后进行 NMR 代谢组学和 RNA 测序分析。缺失导致明显的代谢组失调。短期水杨酸治疗效果虽小，但效果显着，可将乙酰肉碱和磷酸胆碱浓度恢复至野生型水平，并显示出与嘌呤代谢改变的相关性。 RNA 测序表明，短期双水杨酸治疗除了将能量代谢恢复至野生型水平外，还会影响 PKD 中的细胞增殖和炎症。我们发现水杨酸对 ADPKD 的主要失调过程有积极影响：能量代谢、细胞增殖和炎症，从而提供了对其工作机制的更多见解。