Extra-renal 25-hydroxyvitamin D3-1α-hydroxylase in human health and disease
Extra-renal 25-hydroxyvitamin D3-1α-hydroxylase in human health and disease
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DOI：
10.1016/j.jsbmb.2006.12.078
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发表时间：
2007-03-01
影响因子：
4.1
通讯作者：
Adams, John S.
中科院分区：
文献类型：
--
作者：
Hewison, Martin;Burke, Fiona;Adams, John S.
尽管25-羟基维生素D-3-1 α-羟化酶（1 α-OHase）的异位表达已被认识多年，但这种酶在肾脏外的确切功能仍有待讨论。肾外1 α-羟化酶的三个具体方面引起了最多的关注：（i）正常生理过程中非经典组织中的表达和调节;（ii）对免疫系统和炎症性疾病的影响;（iii）在肿瘤中的表达和功能。肾外1 α-羟化酶活性最公认的表现仍然是在某些肉芽肿性疾病患者中发现的，其中局部合成的1 α，25（OH）（2）D-3有可能溢出到全身循环中。然而，免疫组织化学和mRNA分析表明，1 α-羟化酶也表达的各种正常人体组织，包括胃肠道，皮肤，血管和胎盘。这促进了1，25（OH）（2）D-3的自分泌/旁分泌合成有助于正常生理学的想法，特别是在介导维生素D对先天性（巨噬细胞）和获得性（树突细胞）免疫的有效作用方面。我们已经评估了这些细胞合成1，25（OH）（2）D-3的能力以及自分泌对1 α-羟化酶反应的功能意义。数据表明，1，25（OH）（2）D-3的局部合成可能是许多组织对抗原攻击的首选反应模式。(c)2006年由Elsevier Ltd.出版
Although ectopic expression of 25-hydroxyvitamin D-3-1 alpha-hydroxylase (1 alpha-OHase) has been recognized for many years, the precise function of this enzyme outside the kidney remains open to debate. Three specific aspects of extra-renal 1 alpha-OHase have attracted most attention: (i) expression and regulation in non-classical tissues during normal physiology; (ii) effects on the immune system and inflammatory disease; (iii) expression and function in tumors. The most well-recognized manifestation of extra-renal 1 alpha-OHase activity remains that found in some patients with granulomatous diseases where locally synthesized 1 alpha,25(OH)(2)D-3 has the potential to spill-over into the general circulation. However, immunohistochemistry and mRNA analyses suggest that 1 alpha-OHase is also expressed by a variety of normal human tissues including the gastrointestinal tract, skin, vasculature and placenta. This has promoted the idea that autocrine/paracrine synthesis of 1,25(OH)(2)D-3 contributes to normal physiology, particularly in mediating the potent effects of vitamin D on innate (macrophage) and acquired (dendritic cell) immunity. We have assessed the capacity for synthesis of 1,25(OH)(2)D-3 in these cells and the functional significance of autocrine responses to 1 alpha-hydroxylase. Data suggest that local synthesis of 1,25(OH)(2)D-3 may be a preferred mode of response to antigenic challenge in many tissues. (c) 2006 Published by Elsevier Ltd.