Calcium-sensing receptor expression is regulated by glial cells missing-2 in human parathyroid cells

人甲状旁腺细胞中钙敏感受体的表达受神经胶质细胞missing-2的调节

• 批准号: 20790598
• 负责人: MIZOBUCHI Masahide
• 金额: $ 2.66万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790598/
• 关键词: 二次性副甲状腺機能亢進症; Gcm2; 副甲状腺細胞; Ca感知受容体; ビタミンD受容体; グリアルセルミッシング2; カルシウム感知受容体

Glial cells missing-2 (Gcm2) is the key regulating transcription factor for parathyroid gland development. The role of Gcm2 in parathyroid cell physiology, however, has not been fully studied. In this study, we examined the effects of Gcm2 silencing on cultured human parathyroid cells. Collagenase-dispersed human parathyroid cells from patients with chronic kidney disease were infected with lentivirus expressing shRNA for human Gcm2. Seventy-two hours after infection, mRNA was processed and analyzed for Gcm2, PTH, vitamin D receptor (VDR), calcium-sensing receptor (CaR), 25-hydroxyvitamin D3 1-a-hydroxylase (1-OHase), and proliferating cell nuclear antigen (PCNA) by real-time PCR (qPCR). CaR mRNA and protein were significantly reduced by Gcm2 silencing, however, VDR, PTH, 1-OHase, and PCNA were not significantly affected. Further analysis of CaR mRNA indicated that transcripts containing exon 1B, derived by transcription from CaR promoter 2, were downregulated by Gcm2 silencing. These results indicate that one function of Gcm2 is to maintain high levels of CaR expression in parathyroid cells.

胶质细胞缺失-2 （Glial cells missing-2, Gcm2）是甲状旁腺发育的关键调控转录因子。然而，Gcm2在甲状旁腺细胞生理学中的作用尚未得到充分研究。在这项研究中，我们检测了Gcm2沉默对培养的人甲状旁腺细胞的影响。用表达人Gcm2 shRNA的慢病毒感染慢性肾病患者的胶原酶分散的人甲状旁腺细胞。感染72 h后，采用实时荧光定量PCR （qPCR）对mRNA进行处理，分析Gcm2、PTH、维生素D受体（VDR）、钙敏感受体（CaR）、25-羟基维生素D3 1-a-羟化酶（1- oase）、增殖细胞核抗原（PCNA）的表达。Gcm2沉默后，CaR mRNA和蛋白水平显著降低，而VDR、PTH、1- oase和PCNA水平未受显著影响。对CaR mRNA的进一步分析表明，含有外显子1B的转录本（由CaR启动子2转录而来）因Gcm2沉默而下调。这些结果表明Gcm2的一个功能是在甲状旁腺细胞中维持高水平的CaR表达。

项目成果

Calcium-Sensing Receptor Expression Is Regulated by Glial Cells Missing-2 in Human Parathyroid Cells

• DOI: 10.1359/jbmr.090211
• 发表时间: 2009-07-01
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Mizobuchi, Masahide;Ritter, Cynthia S.;Brown, Alex J.
• 通讯作者: Brown, Alex J.

Effect of elastin degradation on the mineralization of vascular smooth muscle cells

弹性蛋白降解对血管平滑肌细胞矿化的影响

• 发表时间: 2008
• 作者: Hasaka N;Mizobuchi M;et.al.
• 通讯作者: et.al.

Regulation of calcium-sensing receptor by glial cells missing 2 in hyperplastic parathyroid cells

增生性甲状旁腺细胞中缺失2的神经胶质细胞对钙敏感受体的调节

• 发表时间: 2007
• 作者: Hasaka N;Mizobuchi M;et.al.;溝渕正英
• 通讯作者: 溝渕正英