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Previously, we demonstrated that NF-\u03baB activation contributed to parathyroid cell proliferation in rats with chronic kidney disease. Although vitamin D inhibits inflammation and ameliorates SHPT, the contribution of vitamin D deficiency to SHPT via local NF-\u03baB activation remains to be clarified. PTGs collected from 10 uremic patients with advanced SHPT were used to test the expressions of vitamin D receptor (VDR), NF-\u03baB, and proliferating cell nuclear antigen (PCNA). Freshly excised PTG tissues were incubated for 24 hours in vitro with VDR activator (VDRA) calcitriol or NF-\u03baB inhibitor pyrrolidine thiocarbamate (PDTC). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate the regulation of PTH transcription by NF-\u03baB. We found higher levels of activated NF-\u03baB and lower expression of VDR in nodular hyperplastic PTGs than in diffuse hyperplasia. In cultured PTG tissues, treatment with VDRA or PDTC inhibited NF-\u03baB activation and PCNA expression, and downregulated preproPTH mRNA and intact PTH levels. ChIP assays demonstrated the presence of NF-\u03baB binding sites in PTH promoter. Furthermore, in luciferase reporter assays, addition of exogenous p65 significantly increased PTH luciferase activity by 2.4-fold (P &amp;lt; 0.01), while mutation of NF-\u03baB binding site at position \u2212908 of the PTH promoter suppressed p65-induced PTH reporter activity (P &amp;lt; 0.01). In summary, local NF-\u03baB activation contributes to SHPT and mediates the transcriptional activation of PTH directly in uremic patients. Vitamin D deficiency may be involved in SHPT via the activation of NF-\u03baB pathway.<\/jats:p>","DOI":"10.1210\/endocr\/bqab084","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T04:10:53Z","timestamp":1619669453000},"source":"Crossref","is-referenced-by-count":12,"title":["Local NF-\u03baB Activation Promotes Parathyroid Hormone Synthesis and Secretion in Uremic Patients"],"prefix":"10.1210","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9371-6192","authenticated-orcid":false,"given":"Jianping","family":"Mao","sequence":"first","affiliation":[{"name":"Division of Nephrology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, National Clinical Research Center for Aging and 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