Abstract
Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA), acting through nuclear retinoic acid receptors (RARs), is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality. RA signaling appears to be essential for expression of genes involved in developmental hematopoiesis, regulating the endothelial/blood cells balance in the yolk sac, promoting the hemogenic program in the aorta-gonad-mesonephros area and stimulating eryrthropoiesis in fetal liver by activating the expression of erythropoietin. In adults, RA signaling regulates differentiation of granulocytes and enhances erythropoiesis. Vitamin A may facilitate iron absorption and metabolism to prevent anemia and plays a key role in mucosal immune responses, modulating the function of regulatory T cells. Furthermore, defective RA/RARα signaling is involved in the pathogenesis of acute promyelocytic leukemia due to a failure in differentiation of promyelocytes. This review focuses on the different roles played by vitamin A/RA signaling in physiological and pathological mouse hematopoiesis duddurring both, embryonic and adult life, and the consequences of vitamin A deficiency for the blood system.
Highlights
Vitamin A was discovered in the second decade of the twentieth century by Elmer McCollum and Marguerite Davis [1]; known as retinol, it is one of the fat soluble vitamins, and plays an important role in vision, reproduction, immune function, as well as cell growth and communication [2,3,4,5,6,7,8,9,10].Vitamin A, regarded as an important micronutrient in mammalian diet, exists in three forms: retinal, retinol and retinoic acid (RA), the latter being the most metabolically active
RA signaling is crucially involved review we aim to provide the readers with an update on the functions played by vitamin A/RA
Researchers have become increasingly interested in the multiple functions played by vitamin A/RA signaling in developmental and adult hematopoiesis
Summary
Vitamin A was discovered in the second decade of the twentieth century by Elmer McCollum and Marguerite Davis [1]; known as retinol, it is one of the fat soluble vitamins, and plays an important role in vision, reproduction, immune function, as well as cell growth and communication [2,3,4,5,6,7,8,9,10]. RA signaling is crucially involved in the consequences of this deficiency (e.g., xerophthalmia), anemia and immune deficiency highlight other pathogenesis and in the treatment of some types of leukemia [18,19] For these reasons, in this critical roles of vitamin A/RA signaling [5,6]. Mesoderm these clusters clustersconnect connectwith with the developing vessels of the embryo These primitive erythroid cells are soon replaced by a second wave of hematopoiesis, when hematopoietic progenitors and the definitive hematopoietic stem cells (HSC) arise from hemogenic hematopoietic progenitors and the definitive hematopoietic stem cells (HSC) arise from hemogenic endothelial cells [21,22,23]. Follows, we will describe how signaling by RA acts in the main hematopoietic sites: yolk sac, AGM, we will describe how signaling by RA fetal liver and placenta
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