Emerging roles for retinoids in regeneration and differentiation in normal and disease states.
Emerging roles for retinoids in regeneration and differentiation in normal and disease states.
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DOI：
10.1016/j.bbalip.2011.08.002
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Gudas LJ
中科院分区：
文献类型：
--
作者：
Gudas LJ
维生素A（视黄醇）代谢产物全反式维甲酸（RA）是一种信号分子，在身体计划的发展中起着关键作用，并诱导许多类型细胞的分化。本文综述了类维生素A（视黄醇及其代谢产物）在成熟动物中的生理和病理生理作用。在发育中的胚胎和成人中，通过组合Hox基因表达的RA信号传导对于细胞位置记忆是重要的。T细胞成熟/分化需要RA的基因才刚刚开始编目，但很明显，类维生素A在免疫系统中关键基因的表达中起着重要作用。再生研究的一个令人兴奋的，最近的出版物表明，ALDH 1a 2（RALDH 2），这是从视黄醇生产RA的限速酶，是高度诱导后不久截肢再生的心脏，成年鳍，和幼鳍在斑马鱼。因此，当地一代的RA大概起着关键作用，在鳍的形成过程中胚胎发育和鳍再生。HIV转基因小鼠和患有HIV相关肾病的人类患者显示肾小球中RARβ蛋白水平显著降低，HIV转基因小鼠显示视黄醇脱氢酶水平降低，伴随着肾小球中内源性RA水平降低3倍以上。在肺、肾和中枢神经系统的许多不同疾病中，内源性类维生素A（由细胞内的视黄醇合成的类维生素A）的水平发生改变，从而导致病理生理学。
The vitamin A (retinol) metabolite, all-trans retinoic acid (RA), is a signaling molecule that plays key roles in the development of the body plan and induces the differentiation of many types of cells. In this review the physiological and pathophysiological roles of retinoids (retinol and related metabolites) in mature animals are discussed. Both in the developing embryo and in the adult, RA signaling via combinatorial Hox gene expression is important for cell positional memory. The genes that require RA for the maturation/differentiation of T cells are only beginning to be catalogued, but it is clear that retinoids play a major role in expression of key genes in the immune system. An exciting, recent publication in regeneration research shows that ALDH1a2 (RALDH2), which is the rate-limiting enzyme in the production of RA from retinaldehyde, is highly induced shortly after amputation in the regenerating heart, adult fin, and larval fin in zebrafish. Thus, local generation of RA presumably plays a key role in fin formation during both embryogenesis and in fin regeneration. HIV transgenic mice and human patients with HIV-associated kidney disease exhibit a profound reduction in the level of RARβ protein in the glomeruli, and HIV transgenic mice show reduced retinol dehydrogenase levels, concomitant with a greater than 3-fold reduction in endogenous RA levels in the glomeruli. Levels of endogenous retinoids (those synthesized from retinol within cells) are altered in many different diseases in the lung, kidney, and central nervous system, contributing to pathophysiology.
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