Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo, Japan.
Endocr J. 2010;57(2):153-9. doi: 10.1507/endocrj.k09e-321. Epub 2009 Dec 1.
To investigate genes modulated in the parathyroid glands by calcium, expression levels of mRNA for all genes expressed in parathyroid tissue explants (PTEs) obtained from patients with primary hyperparathyroidism (I degrees -HPT) were analyzed by oligo-DNA microarray. PTEs obtained from 4 patients with I degrees -HPT were precultured in normocalcemic medium (Ca(++) 1.0-1.1 mM) for 7 days and then cultured in hypocalcemic medium (Ca(++) 0.60 mM) or hypercalcemic (Ca(++) 1.60 mM) medium containing 4 mg/dl phosphate for an additional 7 days. As expected, expression levels of mRNA for PTH and chromogranin A were decreased to less than 50% in the hypercalcemic medium when compared with those in the hypocalcemic medium. Furthermore, oligo-DNA microarray analyses revealed that 7 genes were up-regulated by more than 2-fold and more than 30 genes were down-regulated by more than 1/2 in PTEs. Interestingly, 9 of these genes (up-regulated genes: chemokine ligand 8, multiple C2 domain and transmembrane region protein 1; down-regulated genes: matrix metallopeptidase-9, B-box and SPRY domain-containing protein, nitric oxide synthase 2A, PTH, cartilage acidic protein 1, chromogranin A, and fibrin 1) were involved in calcium metabolism or calcium-signaling pathways in the parathyroid tissue. However, the expression level of mRNA for alpha-klotho was variable, and it was not constantly decreased in hypercalcemic medium under the present experimental conditions. Although it was not possible to use normal parathyroid tissue, this is the first reported study to have investigated the expression levels of mRNA for all genes in human parathyroid adenomas that are modulated by high calcium concentration in organ culture.
为了研究钙调节甲状旁腺中的基因，通过寡核苷酸 DNA 微阵列分析了从原发性甲状旁腺功能亢进症（I 度-HPT）患者获得的甲状旁腺组织外植体（PTE）中所有基因表达的 mRNA 表达水平。将 4 名 I 度-HPT 患者的 PTE 预先在正常钙培养基（Ca(++)1.0-1.1mM）中培养 7 天，然后在低钙培养基（Ca(++)0.60mM）或高钙培养基（Ca(++)1.60mM）中培养）含有 4mg/dl 磷酸盐再培养 7 天。正如预期的那样，与低钙培养基相比，高钙培养基中 PTH 和嗜铬粒蛋白 A 的 mRNA 表达水平降低至小于 50%。此外，寡核苷酸 DNA 微阵列分析显示，7 个基因的表达水平上调了 2 倍以上，30 多个基因下调了 1/2 以上。有趣的是，这些基因中有 9 个（上调基因：趋化因子配体 8、多个 C2 结构域和跨膜区蛋白 1；下调基因：基质金属蛋白酶-9、B 盒和 SPRY 结构域包含蛋白、一氧化氮合酶 2A、PTH、软骨酸性蛋白 1、嗜铬粒蛋白 A 和纤维蛋白 1）参与甲状旁腺组织中的钙代谢或钙信号通路。然而，α-klotho 的 mRNA 表达水平是可变的，在本实验条件下，高钙培养基中它并没有持续降低。尽管无法使用正常的甲状旁腺组织，但这是第一项研究报告，研究了器官培养中高钙浓度调节的人类甲状旁腺腺瘤中所有基因的 mRNA 表达水平。
