Physiologic and pathophysiologic roles of extra renal CYP27b1: Case report and review.
Physiologic and pathophysiologic roles of extra renal CYP27b1: Case report and review.
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DOI：
10.1016/j.bonr.2018.02.004
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发表时间：
2018-06
期刊：
影响因子：
2.5
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Bikle DD;Patzek S;Wang Y
虽然肾脏最初被认为是通过酶 CYP27b1 产生 1,25(OH)2D 的唯一器官，但现在人们认识到 CYP27b1 在肾脏以外的组织中表达广泛。然而，肾脏是循环 1,25(OH)2D 的主要来源。只有在某些肉芽肿性疾病（如结节病）中，肾外组织才会产生足够的 1,25(OH)2D 来提高循环水平，通常与高钙血症相关，如本综述之前的病例报告所示。因此，正常情况下 CYP27b1 在肾外的表达引出了一个问题，特别是肾外产生的 1,25(OH)2D 是否具有生理重要性。本章将讨论这个问题。首先我们讨论肾外 1,25(OH)2D 产生的位点。接下来讨论了肾外组织中 CYP27b1 表达和活性的调节，指出这种调节是组织特异性的，并且与肾脏中 CYP27b1 的调节不同。最后检查了肾外 1,25(OH)2D3 产生的生理意义，特别关注 CYP27b1 在调节细胞增殖和分化、激素分泌和免疫功能中的作用。目前的数据并没有清楚地证明 CYP27b1 表达在肾脏以外的任何组织中的重要作用，但提供了几个指向这个方向的例子。随着小鼠能够实现 CYP27b1 的组织特异性删除，现在可以明确地解决正常和病理状态下肾外 CYP27b1 表达的作用。
Although the kidney was initially thought to be the sole organ responsible for the production of 1,25(OH)2D via the enzyme CYP27b1, it is now appreciated that the expression of CYP27b1 in tissues other than the kidney is wide spread. However, the kidney is the major source for circulating 1,25(OH)2D. Only in certain granulomatous diseases such as sarcoidosis does the extra renal tissue produce sufficient 1,25(OH)2D to contribute to the circulating levels, generally associated with hypercalcemia, as illustrated by the case report preceding the review. Therefore the expression of CYP27b1 outside the kidney under normal circumstances begs the question why, and in particular whether the extra renal production of 1,25(OH)2D has physiologic importance. In this chapter this question will be discussed. First we discuss the sites for extra renal 1,25(OH)2D production. This is followed by a discussion of the regulation of CYP27b1 expression and activity in extra renal tissues, pointing out that such regulation is tissue specific and different from that of CYP27b1 in the kidney. Finally the physiologic significance of extra renal 1,25(OH)2D3 production is examined, with special focus on the role of CYP27b1 in regulation of cellular proliferation and differentiation, hormone secretion, and immune function. At this point the data do not clearly demonstrate an essential role for CYP27b1 expression in any tissue outside the kidney, but several examples pointing in this direction are provided. With the availability of the mouse enabling tissue specific deletion of CYP27b1, the role of extra renal CYP27b1 expression in normal and pathologic states can now be addressed definitively.