{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:17:50Z","timestamp":1791415070302,"version":"4.3.3"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2025,3,28]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Pathological cardiac hypertrophy can result in heart failure. Protein dephosphorylation plays a primary role in the mediation of various cellular processes in cardiomyocytes. Here, we investigated the effects of a protein tyrosine phosphatase, PRL2 (phosphatase of regenerative liver 2), on pathological cardiac hypertrophy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>The PRL2 knockout mice were subjected to angiotensin II infusion or transverse aortic constriction to induce myocardial hypertrophy and cardiac dysfunction. RNA-sequencing analysis was performed to explore the underlying mechanisms. Mass spectrometry and bio-layer interferometry assays were used to identify AMPK\u03b12 (AMP-activated protein kinase \u03b12) as an interacting protein of PRL2. Mutant plasmids of AMPK\u03b12 were used to clarify how PRL2 interacts and dephosphorylates AMPK\u03b12.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              A significant upregulation of PRL2 was observed in hypertrophic myocardium tissues in mice and patients with heart failure. PRL2 deficiency alleviated cardiac hypertrophy, fibrosis, and dysfunction in mice challenged with angiotensin II infusion or transverse aortic constriction. Transcriptomic and biochemical analyses showed that PRL2 knockout or silence maintained AMPK\n              <jats:sup>T172<\/jats:sup>\n              phosphorylation and subsequent mitochondrial integrity in angiotensin II-challenged heart tissues or cardiomyocytes. Mass spectrometry-based interactome assay indicated AMPK\u03b12 subunit as the substrate of PRL2. Mechanistically, PRL2 binds to the C-terminal domain of AMPK\u03b12 and then dephosphorylates AMPK\u03b12\n              <jats:sup>T172<\/jats:sup>\n              via its active site C46. Adeno-associated virus 9-mediated deficiency of cardiomyocyte PRL2 also protected cardiac mitochondrial function and showed cardioprotective effects in angiotensin II-challenged mice, but these benefits were not observed in AMPK\u03b12\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>This study reveals that PRL2, as a novel AMPK-regulating phosphatase, promotes mitochondrial instability and hypertrophic injury in cardiomyocytes and provides PLR2 as a potential target for future drug development treating heart failure.<\/jats:p>\n          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University, Zhejiang, China (X.H., S.Y., B.Y., G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaojuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Laboratory Animals and Safety Research (X.H., Q.S., Y.T., J.Z., W.L., Y.L., R.Z., J.W., H.Y.), Hangzhou Medical College, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Laboratory Animals and Safety Research (X.H., Q.S., Y.T., J.Z., W.L., Y.L., R.Z., J.W., H.Y.), Hangzhou Medical College, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Laboratory Animals and Safety Research (X.H., Q.S., Y.T., J.Z., W.L., Y.L., R.Z., J.W., H.Y.), Hangzhou Medical College, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Pharmacy, Beihua University, Jilin, China (M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Li","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Laboratory Animals and Safety Research (X.H., Q.S., Y.T., J.Z., W.L., Y.L., R.Z., J.W., H.Y.), Hangzhou Medical College, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Laboratory Animals and Safety Research (X.H., Q.S., Y.T., J.Z., W.L., Y.L., R.Z., J.W., H.Y.), Hangzhou Medical College, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Zhejiang 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