title: Cyclooxygenase 2 promotes parathyroid hyperplasia in ESRD.
abstract: Hyperplasia of the PTG underlies the secondary hyperparathyroidism (SHPT) observed in CKD, but the mechanism underlying this hyperplasia is incompletely understood. Because aberrant cyclooxygenase 2 (COX2) expression promotes epithelial cell proliferation, we examined the effects of COX2 on the parathyroid gland in uremia. In patients with ESRD who underwent parathyroidectomy, clusters of cells within the parathyroid glands had increased COX2 expression. Some COX2-positive cells exhibited two nuclei, consistent with proliferation. Furthermore, nearly 78% of COX2-positive cells expressed proliferating cell nuclear antigen (PCNA). In the 5/6-nephrectomy rat model, rats fed a high-phosphate diet had significantly higher serum PTH levels and larger parathyroid glands than sham-operated rats. Compared with controls, the parathyroid glands of uremic rats exhibited more PCNA-positive cells and greater COX2 expression in the chief cells. Treatment with COX2 inhibitor celecoxib significantly reduced PCNA expression, attenuated serum PTH levels, and reduced the size of the glands. In conclusion, COX2 promotes the pathogenesis of hyperparathyroidism in ESRD, suggesting that inhibiting the COX2 pathway could be a potential therapeutic target.
authors.affiliation: Division of Nephrology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Junsi
authors.initials: J
authors.lastname: Qiu
authors.forename: Haiming
authors.initials: H
authors.lastname: Li
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Lu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.forename: Junwei
authors.initials: J
authors.lastname: Yang
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Wang
authors.forename: Liyin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.forename: Chuan-Ming
authors.initials: CM
authors.lastname: Hao
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
mesh_terms: D000328:Adult; D000818:Animals; D000068579:Celecoxib; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010281:Parathyroid Hormone / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D006435:Renal Dialysis; D012189:Retrospective Studies; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D010281:Parathyroid Hormone; D018809:Proliferating Cell Nuclear Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib