Retinoids and nephron mass control

Abstract

Advances in the molecular biology of retinoids have provided evidence that vitamin A profoundly influences the differentiation of the whole embryo. In addition to its well-characterized role in primary body axis and central nervous system formation, vitamin A is also required for the ad hoc development of numerous tissues and organs, including the kidney. This review will focus on the emerging evidence that the development of the urogenital tract depends on retinoids. In order to understand the role of vitamin A during kidney development, the mechanisms and sites of retinoic acid production are presented. In addition, an overview of the molecular targets that may be regulated by retinoic acid is included. Together, these elements support the concept that control of vitamin A homeostasis during renal organogenesis might control nephrogenesis via specific gene expression. The clinical impact of variations in vitamin A status during pregnancy is discussed.

Absence of mutations in the HOXA11 and HOXD11 genes in children with congenital renal malformations

“…Moreover, it has been shown that vitamin A deficiency causes renal anomalies in mice and potentially regulates the expression of HOX genes [16], suggesting that potential environment-gene interaction could produce a similar phenotype, as a result of dietary deficiency, without both copies of both genes having to be deleted.…”

Fetal and Maternal Physiology and Ultrasound Diagnosis

“…Therefore, more and more scientists believe that congenital nephron deficit could be a 'missing link' in understanding of the etiology of essential hypertension. 131 For many years, data on fetal renal function have been insufficient and indirect. Investigations were carried out mainly in experimental animals and aborted fetuses.…”

“…Since the lack of nephrons after birth is unrecoverable, numerous studies have been conducted to detect factors that in some way may impair the process of nephrogenesis. 131 Studies conducted on the cell cultures of the fetal kidney showed that retinoids, metabolites of vitamin A, have a significant impact on the number of nephrons and that this effect is dose-dependent. Vitamin A deficiency in pregnant women is rare in developed countries but is more frequently observed in underdeveloped countries as a result of insufficient food intake.…”

“…131 Unfortunately, lack of vitamin A is not the only factor that can lead to a nephron deficit. Experiments on animals have proved that fetal growth retardation, 132 maternal hyperglycemia 133 and some medications, such as gentamicin, 134 cause a reduced number of nephrons, which cannot be fully compensated for after birth.…”

Once and again: Retinoic acid signaling in the developing and regenerating olfactory pathway

“…Retinoic acid (RA), 13-cis retinoic acid (the active retinoid in the antiacne pharmaceutical Accutane), retinol (vitamin A, the primary dietary precursor of RA), and other retinoids including retinaldehydes like 11-cis retinal (the chromophore associated with rhodopsin) influence a broad range of physiological and pathological processes (reviewed by Pfahl and Chytil, 1996;Gilbert and Merlet-Benichou, 2000;Reifen, 2002;Maden, 2002;Biesalski and Nohr, 2003;Bonet et al, 2003;Wang, 2003). The physiological significance of retinoids was originally inferred from the relationship between dietary deprivation or excess intake of vitamin A and pathologies as diverse as hepatoxicity, carcinogenesis, psychosis, and blindness (reviewed by Underwood, 2004).…”