{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:50:30Z","timestamp":1792025430895,"version":"4.4.0"},"reference-count":80,"publisher":"Portland Press Ltd.","issue":"20","license":[{"start":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T00:00:00Z","timestamp":1633651200000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>AMP-activated protein kinase (AMPK) plays a key role in the cellular response to low energy stress and has emerged as an attractive therapeutic target for tackling metabolic diseases. Whilst significant progress has been made regarding the physiological role of AMPK, its function in the kidney remains only partially understood. We use a mouse model expressing a constitutively active mutant of AMPK to investigate the effect of AMPK activation on kidney function in vivo. Kidney morphology and changes in gene and protein expression were monitored and serum and urine markers were measured to assess kidney function in vivo. Global AMPK activation resulted in an early-onset polycystic kidney phenotype, featuring collecting duct cysts and compromised renal function in adult mice. Mechanistically, the cystic kidneys had increased cAMP levels and ERK activation, increased hexokinase I (Hk I) expression, glycogen accumulation and altered expression of proteins associated with autophagy. Kidney tubule-specific activation of AMPK also resulted in a polycystic phenotype, demonstrating that renal tubular AMPK activation caused the cystogenesis. Importantly, human autosomal dominant polycystic kidney disease (ADPKD) kidney sections revealed similar protein localisation patterns to that observed in the murine cystic kidneys. Our findings show that early-onset chronic AMPK activation leads to a polycystic kidney phenotype, suggesting dysregulated AMPK signalling is a contributing factor in cystogenesis.<\/jats:p>","DOI":"10.1042\/cs20210821","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T10:02:45Z","timestamp":1633687365000},"page":"2393-2408","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Chronic activation of AMP-activated protein kinase leads to early-onset polycystic kidney phenotype"],"prefix":"10.1042","volume":"135","author":[{"given":"Laura","family":"Wilson","sequence":"first","affiliation":[{"name":"MRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Imperial College London, W12 0NN U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice\u00a0E.","family":"Pollard","sequence":"additional","affiliation":[{"name":"MRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Imperial College London, W12 0NN U.K."},{"name":"Structure Biophysics and Fragments, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Penfold","sequence":"additional","affiliation":[{"name":"MRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Imperial College London, W12 0NN U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip\u00a0J.","family":"Muckett","sequence":"additional","affiliation":[{"name":"MRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Imperial College London, W12 0NN U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Whilding","sequence":"additional","affiliation":[{"name":"MRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Imperial College London, W12 0NN U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Bohlooly-Y.","sequence":"additional","affiliation":[{"name":"Translational Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Wilson","sequence":"additional","affiliation":[{"name":"Centre for Nephrology, UCL Department of Renal Medicine, Royal Free Campus, London NW3 2PF, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2316-1830","authenticated-orcid":false,"given":"David","family":"Carling","sequence":"additional","affiliation":[{"name":"MRC London Institute of Medical Sciences, Hammersmith Hospital Campus, Imperial College London, W12 0NN U.K."},{"name":"Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"2021113011240656400_B1","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41573-019-0019-2","article-title":"AMP-activated protein kinase: the current landscape for drug development","volume":"18","author":"Steinberg","year":"2019","journal-title":"Nat. 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