Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis
Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis
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DOI：
10.1073/pnas.1011498108
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发表时间：
2011-02-08
影响因子：
11.1
通讯作者：
Caplan, Michael J.
中科院分区：
文献类型：
--
作者：
Takiar, Vinita;Nishio, Saori;Caplan, Michael J.
Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves both fluid secretion and abnormal proliferation of cyst-lining epithelial cells. The chloride channel of the cystic fibrosis transmembrane conductance regulator (CFTR) participates in secretion of cyst fluid, and the mammalian target of rapamycin (mTOR) pathway may drive proliferation of cyst epithelial cells. CFTR and mTOR are both negatively regulated by AMP-activated protein kinase (AMPK). Metformin, a drug in wide clinical use, is a pharmacological activator of AMPK. We find that metformin stimulates AMPK, resulting in inhibition of both CFTR and the mTOR pathways. Metformin induces significant arrest of cystic growth in both in vitro and ex vivo models of renal cystogenesis. In addition, metformin administration produces a significant decrease in the cystic index in two mouse models of ADPKD. Our results suggest a possible role for AMPK activation in slowing renal cystogenesis as well as the potential for therapeutic application of metformin in the context of ADPKD.
