Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.
J Clin Invest. 2009 Oct;119(10):2887-91. doi: 10.1172/JCI40784. Epub 2009 Sep 21.
Secondary hyperparathyroidism often occurs in chronic kidney disease (CKD) and vitamin D deficiency, resulting in increased fractures and mortality. Understanding factors that stimulate parathyroid hormone (PTH) synthesis is important for devising methods to treat this condition. Previous work has demonstrated that murine Pth mRNA levels are regulated by proteins that bind AU-rich elements (AREs) within the 3' UTR region of Pth mRNA and influence Pth mRNA stability. In this issue of the JCI, Nechama et al. demonstrate that in murine secondary hyperparathyroidism associated with CKD or Ca deficiency, the activity of Pin1, a peptidyl-prolyl isomerase, is reduced (see the related article beginning on page 3102). Reduced Pin1 activity resulted in the phosphorylation and degradation of an ARE-binding protein, K-homology splicing regulator protein (KSRP), which normally enhances the degradation of Pth mRNA. The activity of other ARE-binding proteins, such as AU-rich binding factor 1 (AUF1), that increase Pth mRNA stability, was increased, thereby increasing PTH synthesis. This work suggests new ways by which to regulate PTH synthesis in secondary hyperparathyroidism.
继发性甲状旁腺功能亢进症常发生于慢性肾脏病（CKD）和维生素 D 缺乏症，导致骨折和死亡率增加。了解刺激甲状旁腺激素（PTH）合成的因素对于制定治疗这种疾病的方法很重要。以前的工作已经表明，鼠 Pth mRNA 水平受到结合 Pth mRNA 3'UTR 区域内富含 AU 元件（AREs）的蛋白的调节，影响 Pth mRNA 的稳定性。在本期 JCI 中，Nechama 等人证明，在与 CKD 或钙缺乏相关的鼠继发性甲状旁腺功能亢进症中，肽基脯氨酰顺反异构酶 Pin1 的活性降低（见第 3102 页开始的相关文章）。Pin1 活性降低导致 ARE 结合蛋白 K-homology 剪接调节蛋白（KSRP）的磷酸化和降解，而 KSRP 通常会增强 Pth mRNA 的降解。增加 Pth mRNA 稳定性的其他 ARE 结合蛋白（如 AU 丰富结合因子 1（AUF1））的活性增加，从而增加 PTH 合成。这项工作为调节继发性甲状旁腺功能亢进症中的 PTH 合成提供了新的途径。
