Role of vitamin A in determining nephron mass and possible relationship to hypertension
Role of vitamin A in determining nephron mass and possible relationship to hypertension
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DOI：
10.1093/jn/138.8.1407
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发表时间：
2008-08-01
影响因子：
4.2
通讯作者：
Manolescu, Daniel-Constantin
中科院分区：
文献类型：
--
作者：
Bhat, Pangala V.;Manolescu, Daniel-Constantin
维生素A（视黄醇）及其类似物（类维生素A）是细胞增殖、分化、免疫功能和凋亡的重要调节剂。肾脏是维生素A作用的靶器官。维甲酸（RA）是一种维生素A代谢产物，通过调控受体酪氨酸激酶的表达参与胚胎肾脏的形成，从而调节输尿管芽的分支形态发生。母亲的维生素A状况深刻地影响新生儿的肾器官形成。在啮齿类动物中，轻度维生素A缺乏导致肾单位数量减少20%。在成年人中，每个肾脏的肾单位数量在0.3到130万之间变化，这是正常的。然而，最近的研究表明，处于肾单位数目低端的人易患原发性高血压。由于RA调节肾单位质量，因此其在肾发生过程中的最佳可用性至关重要。胚胎中的RA水平受多种因素影响，例如母体维生素A营养和视黄醇代谢紊乱。孕妇在怀孕期间缺乏维生素A在发展中国家很普遍，当确定肾单位数量时，这些人口中的一部分可能在胎儿期暴露于低维生素A。婴儿出生时可能有次优的肾单位，并可能在以后的生活中发展为原发性高血压。虽然母体维生素A缺乏症在发达国家并不常见，但先天性肾单位数量差异很大，表明由于将视黄醇转化为RA的酶的常见变体，胎儿RA水平较低。这些婴儿在以后的生活中可能需要加强对高血压的监测。
Vitamin A (retinol) and its analogs (retinoids) are important regulators of cell proliferation, differentiation, immune function, and apoptosis. The kidneys are target organs for vitamin A action. Retinoic acid (RA), a vitamin A metabolite, is involved in embryonic kidney patterning through the control of receptor tyrosine kinase expression, which modulates ureteric bud branching morphogenesis. Vitamin A status of the mother profoundly affects kidney organogenesis of the newborn. In rodents, mild vitamin A deficiency results in a 20% reduction of nephron number. In adult humans, nephron number varies between 0.3 and 1.3 million per kidney, which is accepted as normal. However, recent studies indicate that humans at the low end of nephron number are predisposed to primary hypertension. Because RA regulates nephron mass, its optimal availability during nephrogenesis is critical. RA levels in the embryo are affected by several factors, such as maternal vitamin A nutrition and disturbances in retinol metabolism. Maternal vitamin A deficiency during pregnancy is widespread in developing countries and segments of these populations may be exposed to low vitamin A during fetal life when nephron number is determined. Infants are likely to be born with suboptimal nephrons and may develop primary hypertension later in life. Although maternal vitamin A deficiency is not common in developed countries, congenital nephron number nevertheless varies widely, indicating low fetal RA levels due to common variants of the enzymes that convert retinol to RA. These infants might require heightened surveillance for hypertension later in life.