{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:37:30Z","timestamp":1788316650198,"version":"build-2803163510"},"reference-count":150,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["ISF 642\/16"],"award-info":[{"award-number":["ISF 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":["ISF 2030\/21"],"award-info":[{"award-number":["ISF 2030\/21"]}],"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":["BSF 2019300"],"award-info":[{"award-number":["BSF 2019300"]}],"id":[{"id":"10.13039\/100006221","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that induces morbidity and mortality in patients. How CKD stimulates the parathyroid to increase parathyroid hormone (PTH) secretion, gene expression and cell proliferation remains an open question. In experimental SHP, the increased PTH gene expression is post-transcriptional and mediated by PTH mRNA\u2013protein interactions that promote PTH mRNA stability. These interactions are orchestrated by the isomerase Pin1. Pin1 participates in conformational change-based regulation of target proteins, including mRNA-binding proteins. In SHP, Pin1 isomerase activity is decreased, and thus, the Pin1 target and PTH mRNA destabilizing protein KSRP fails to bind PTH mRNA, increasing PTH mRNA stability and levels. An additional level of post-transcriptional regulation is mediated by microRNA (miRNA). Mice with parathyroid-specific knockout of Dicer, which facilitates the final step in miRNA maturation, lack parathyroid miRNAs but have normal PTH and calcium levels. Surprisingly, these mice fail to increase serum PTH in response to hypocalcemia or uremia, indicating a role for miRNAs in parathyroid stimulation. SHP often leads to parathyroid hyperplasia. Reduced expressions of parathyroid regulating receptors, activation of transforming growth factor \u03b1-epidermal growth factor receptor, cyclooxygenase 2-prostaglandin E2 and mTOR signaling all contribute to the enhanced parathyroid cell proliferation. Inhibition of mTOR by rapamycin prevents and corrects the increased parathyroid cell proliferation of SHP. This review summarizes the current knowledge on the mechanisms that stimulate the parathyroid cell at multiple levels in SHP.<\/jats:p>","DOI":"10.3390\/metabo12020111","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T20:40:18Z","timestamp":1643143218000},"page":"111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Molecular Mechanisms of Parathyroid Disorders in Chronic Kidney Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Alia","family":"Hassan","sequence":"first","affiliation":[{"name":"Minerva Center for Bone and Mineral Research, Nephrology Services, Hadassah\u2014Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nareman","family":"Khalaily","sequence":"additional","affiliation":[{"name":"Minerva Center for Bone and Mineral Research, Nephrology Services, Hadassah\u2014Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Kilav-Levin","sequence":"additional","affiliation":[{"name":"Minerva Center for Bone and Mineral Research, Nephrology Services, Hadassah\u2014Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"Nursing, Jerusalem College of Technology, Jerusalem 91160, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morris","family":"Nechama","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Hadassah\u2014Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"The Wohl Institute for Translational Medicine, Hadassah\u2014Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oded","family":"Volovelsky","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Hadassah\u2014Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"The Wohl Institute for Translational Medicine, Hadassah\u2014Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Silver","sequence":"additional","affiliation":[{"name":"Minerva Center for Bone and Mineral Research, Nephrology Services, Hadassah\u2014Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0903-8182","authenticated-orcid":false,"given":"Tally","family":"Naveh-Many","sequence":"additional","affiliation":[{"name":"Minerva Center for Bone and Mineral Research, Nephrology Services, Hadassah\u2014Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"The Wohl Institute for Translational Medicine, Hadassah\u2014Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41574-018-0115-0","article-title":"The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases","volume":"15","author":"Hannan","year":"2019","journal-title":"Nat. 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