{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:19:33Z","timestamp":1793049573834,"version":"4.5.0"},"reference-count":49,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Natural Science Foundation of Jiangsu Province for Distinguished Young Scholars","award":["BK20200004"],"award-info":[{"award-number":["BK20200004"]}]},{"name":"National Key Research and Development Program of China","award":["2018YFA0900803"],"award-info":[{"award-number":["2018YFA0900803"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["3217080376,81900583,81770630,31870912,31771560,31670883,8210140220,81570583"],"award-info":[{"award-number":["3217080376,81900583,81770630,31870912,31771560,31670883,8210140220,81570583"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["CIFMS2021-I2M-1-047,2021-I2M-1-061,2022-I2M-2-004"],"award-info":[{"award-number":["CIFMS2021-I2M-1-047,2021-I2M-1-061,2022-I2M-2-004"]}]},{"name":"Non-profit Central Research Institute Fund of CAMS","award":["2019PT310028"],"award-info":[{"award-number":["2019PT310028"]}],"id":[{"id":"https:\/\/ror.org\/01wnfae18","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Key Research and Development Program of China","award":["2023YFE0118000"],"award-info":[{"award-number":["2023YFE0118000"]}]},{"name":"Department of Oncology","award":["\/"],"award-info":[{"award-number":["\/"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2023-I2M-2-010"],"award-info":[{"award-number":["2023-I2M-2-010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,8]]},"abstract":"<jats:p>\n                    Acute pancreatitis (AP) is among the most common hospital gastrointestinal diagnoses; understanding the mechanisms underlying the severity of AP is critical for development of new treatment options for this disease. Here, we evaluate the biological function of phosphofructo-2-kinase\/fructose-2,6-biphosphatase 3 (PFKFB3) in AP pathogenesis in 2 independent genetically engineered mouse models of AP. PFKFB3 was elevated in AP and severe AP (SAP), and KO of\n                    <jats:italic>Pfkfb3<\/jats:italic>\n                    abrogated the severity of alcoholic SAP (FAEE-SAP). Using a combination of genetic, pharmacological, and molecular studies, we defined the interaction of PFKFB3 with inositol 1,4,5-trisphosphate receptor (IP3R) as a key event mediating this phenomenon. Further analysis demonstrated that the interaction between PFKFB3 and IP3R promotes FAEE-SAP severity by altering intracellular calcium homeostasis in acinar cells. Together, our results support a PFKFB3-driven mechanism controlling AP pathobiology and define this enzyme as a therapeutic target to ameliorate the severity of this condition.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.169481","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T12:00:52Z","timestamp":1716465652000},"source":"Crossref","is-referenced-by-count":14,"title":["PFKFB3 controls acinar IP3R-mediated Ca2+ overload to regulate acute pancreatitis severity"],"prefix":"10.1172","volume":"9","author":[{"given":"Tan","family":"Zhang","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."},{"name":"National Key Laboratory of Immunity and Inflammation, and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems 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Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuepeng","family":"Jin","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of intelligent Cancer Biomarker Discovery & Translation, Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Immunity and Inflammation, and CAMS Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine (ISM), Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of intelligent Cancer Biomarker 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