{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:44:26Z","timestamp":1790300666191,"version":"4.1.0"},"reference-count":110,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that correlates with morbidity and mortality in uremic patients. It is characterized by high serum parathyroid hormone (PTH) levels and impaired bone and mineral metabolism. The main mechanisms underlying SHP are increased PTH biosynthesis and secretion as well as increased glandular mass. The mechanisms leading to parathyroid cell proliferation in SHP are not fully understood. Reduced expressions of the receptors for calcium and vitamin D contribute to the disinhibition of parathyroid cell proliferation. Activation of transforming growth factor-\u03b1-epidermal growth factor receptor (TGF-\u03b1-EGFR), nuclear factor kappa B (NF-kB), and cyclooxygenase 2- prostaglandin E2 (Cox2-PGE2) signaling all correlate with parathyroid cell proliferation, underlining their roles in the development of SHP. In addition, the mammalian target of rapamycin (mTOR) pathway is activated in parathyroid glands of experimental SHP rats. Inhibition of mTOR by rapamycin prevents and corrects the increased parathyroid cell proliferation of SHP. Mice with parathyroid-specific deletion of all miRNAs have a muted increase in serum PTH and fail to increase parathyroid cell proliferation when challenged by CKD, suggesting that miRNA is also necessary for the development of SHP. This review summarizes the current knowledge on the mechanisms of parathyroid cell proliferation in SHP.<\/jats:p>","DOI":"10.3390\/ijms21124332","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T11:00:56Z","timestamp":1592478056000},"page":"4332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Parathyroid Cell Proliferation in Secondary Hyperparathyroidism of Chronic Kidney Disease"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0903-8182","authenticated-orcid":false,"given":"Tally","family":"Naveh-Many","sequence":"first","affiliation":[{"name":"Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"The Wohl Institute for Translational Medicine, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5378-1045","authenticated-orcid":false,"given":"Oded","family":"Volovelsky","sequence":"additional","affiliation":[{"name":"The Wohl Institute for Translational Medicine, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"Pediatric Nephrology Unit and Research Lab, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/366575a0","article-title":"Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid","volume":"366","author":"Brown","year":"1993","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1111\/j.1523-1755.2005.09501.x","article-title":"Regulation of PTH synthesis and secretion relevant to the management of secondary hyperparathyroidism in chronic kidney disease 2","volume":"67","author":"Silver","year":"2005","journal-title":"Kidney Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"V20","DOI":"10.1093\/ndt\/gfh1052","article-title":"Modulation and action of the calcium-sensing receptor","volume":"19","year":"2004","journal-title":"Nephrol. 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