Journal Article

Parathyroid cell growth in patients with advanced secondary hyperparathyroidism: vitamin D receptor and cyclin‐dependent kinase inhibitors, p21 and p27

Masanori Tokumoto, Kazuhiko Tsuruya, Kyoichi Fukuda, Hidetoshi Kanai, Shoji Kuroki, Hideki Hirakata and Mitsuo Iida

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 18, issue suppl_3, pages iii9-iii12
Published in print June 2003 | ISSN: 0931-0509
Published online June 2003 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfg1003
Parathyroid cell growth in patients with advanced secondary hyperparathyroidism: vitamin D receptor and cyclin‐dependent kinase inhibitors, p21 and p27

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Uraemic patients with advanced secondary hyperparathyroidism (2HPT) have nodular hyperplastic glands with a decreased vitamin D receptor (VDR) density. Previous studies have shown that nodular hyperplasia expressed a significantly lower VDR density as compared with diffuse hyperplasia, and the VDR density negatively correlated with both the glandular weight and the marker of cell proliferation. However, the mechanism by which the decreased VDR density leads to parathyroid cell proliferation remains unclear. In the myelomonocytic cell line, active vitamin D3 is known to activate the transcription of both p21 and p27, cyclin‐dependent kinase inhibitors (CDKIs), regulating the transition from the G1 to the S phase of the cell cycle, in a VDR‐dependent manner. Moreover, the overexpression of p21 and p27 inhibits cell proliferation. In order to elucidate the mechanism of parathyroid cell proliferation, the expression of CDKIs, p21 and p27, and the VDR was analysed immunohistochemically, and compared among nodular and diffuse hyperplastic parathyroid glands, and histologically normal parathyroid glands. The VDR expression in nodular hyperplasias was significantly decreased compared with either diffuse hyperplasias or normal parathyroid glands. The expression of both p21 and p27 was also significantly lower in nodular hyperplasias than in diffuse hyperplasias or normal parathyroid glands. Sections of parathyroid glands with a high expression of nuclear VDR highly expressed both p21 and p27. In nodular hyperplasias, the expression of both p21 and p27 correlated either positively with the nuclear VDR expression or inversely with the glandular weight. Therefore, the reduced expression of p21 and p27, being VDR dependent, is a major pathogenic factor for nodular parathyroid gland growth in advanced 2HPT.

Keywords: cyclin‐dependent kinase inhibitor; haemodialysis; p21; p27; secondary hyperparathyroidism; vitamin D receptor

Journal Article.  2133 words.  Illustrated.

Subjects: Nephrology

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