Authors: Tokumoto M.; Tsuruya K.; Fukuda K.; Kanai H.; Kuroki S.; Hirakata H.; Iida M.

Source: Nephrology Dialysis Transplantation, Volume 18, Number 3, March 2003 , pp. iii9-iii12(4)

Publisher: Oxford University Press

Abstract:

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 D<inf>3</inf> is known to activate the transcription of both p21 and p27, cyclin-dependent kinase inhibitors (CDKIs), regulating the transition from the G<inf>1</inf> 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

Document Type: Research article

DOI: http://dx.doi.org/10.1093/ndt/gfg1003

Affiliations: 1: Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Publication date: 2003-03-01

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• Nephrology Dialysis Transplantation is one of the world's leading journals devoted to original clinical and laboratory research in nephrology, dialysis and transplantation. Published monthly, the journal provides an essential resource for researchers and clinicians throughout the world.

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