{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:10:59Z","timestamp":1789236659330,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["642\/16"],"award-info":[{"award-number":["642\/16"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1487\/23"],"award-info":[{"award-number":["1487\/23"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006221","name":"United States - Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["2019300"],"award-info":[{"award-number":["2019300"]}],"id":[{"id":"10.13039\/100006221","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,11,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Secondary hyperparathyroidism (SHP) associated with chronic kidney disease (CKD) contributes to morbidity and mortality, yet the related parathyroid signaling pathways are not fully understood. Previous studies have indicated that the parathyroid mTORC1 pathway is activated in both experimental CKD and hypocalcemia\u2010induced SHP. Furthermore, mice with parathyroid\u2010specific\n                    <jats:italic>mTOR<\/jats:italic>\n                    deficiency (PT\u2010\n                    <jats:italic>mTOR<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) exhibit disrupted parathyroid glands, but maintain normal serum PTH levels. Conversely, PT\u2010\n                    <jats:italic>Tsc1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, with mTORC1 hyperactivation, have enlarged glands and high serum PTH and calcium levels. We now uncover links between mTORC1 function, parathyroid gland morphology, and the response to CKD. Despite impaired gland structure, PT\u2010\n                    <jats:italic>mTOR<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice increased serum PTH to levels similar to controls in response to CKD, but not to acute kidney injury (AKI), highlighting the adaptability of their parathyroid glands to chronic but not acute stimulation. PT\u2010\n                    <jats:italic>Tsc1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, with enlarged glands also exhibited a CKD\u2010induced rise in serum PTH comparable to controls, but with a reduced magnitude, suggesting compromised secretion capacity. Parathyroid glands from PT\u2010\n                    <jats:italic>Tsc1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice displayed sustained high PTH secretion in culture, with no further increase when exposed to calcium\u2010depleted media, unlike control glands. Complementing these findings, human data from 106 healthcare organizations demonstrated that drug\u2010induced mTORC1 inhibition is associated with reduced serum PTH and a lower incidence of SHP in kidney transplant recipients. Collectively, our findings underscore the complex interplay between mTORC1 signaling and gland structure in the pathogenesis of SHP.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401547rr","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T09:25:26Z","timestamp":1732181126000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The roles of\n                    <scp>mTORC1<\/scp>\n                    in parathyroid gland function in chronic kidney disease\u2010induced secondary hyperparathyroidism: Evidence from male genetic mouse\u00a0models and clinical data"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0698-3303","authenticated-orcid":false,"given":"Nareman","family":"Khalaily","sequence":"first","affiliation":[{"name":"Minerva Center for Bone and Mineral Research, Nephrology Services Hadassah Hebrew University Medical Center and Faculty of Medicine  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2450-9250","authenticated-orcid":false,"given":"Alia","family":"Hassan","sequence":"additional","affiliation":[{"name":"Minerva Center for Bone and Mineral Research, Nephrology Services Hadassah Hebrew University Medical Center and Faculty of Medicine  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3049-838X","authenticated-orcid":false,"given":"Yasmeen","family":"Khream","sequence":"additional","affiliation":[{"name":"Minerva Center for Bone and Mineral Research, Nephrology Services Hadassah Hebrew University Medical Center and Faculty of Medicine  Jerusalem 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