Vitamin A Deficiency and Alterations in the Extracellular Matrix

Abstract

Vitamin A or retinol which is the natural precursor of several biologically active metabolites can be considered the most multifunctional vitamin in mammals. Its deficiency is currently, along with protein malnutrition, the most serious and common nutritional disorder worldwide. It is necessary for normal embryonic development and postnatal tissue homeostasis, and exerts important effects on cell proliferation, differentiation and apoptosis. These actions are produced mainly by regulating the expression of a variety of proteins through transcriptional and non-transcriptional mechanisms. Extracellular matrix proteins are among those whose synthesis is known to be modulated by vitamin A. Retinoic acid, the main biologically active form of vitamin A, influences the expression of collagens, laminins, entactin, fibronectin, elastin and proteoglycans, which are the major components of the extracellular matrix. Consequently, the structure and macromolecular composition of this extracellular compartment is profoundly altered as a result of vitamin A deficiency. As cell behavior, differentiation and apoptosis, and tissue mechanics are influenced by the extracellular matrix, its modifications potentially compromise organ function and may lead to disease. This review focuses on the effects of lack of vitamin A in the extracellular matrix of several organs and discusses possible molecular mechanisms and pathologic implications.

Intracranial elastance is increased in idiopathic intracranial hypertension

“…Along these lines, cell membrane biomechanical properties are profoundly influenced by fatty acid and cholesterol composition [15,16]. Further, given that retinol has been implicated in IIH pathophysiology [4], it is also notable that retinol is known to exert potent influence over regulation of extracellular matrix components, which in turn contribute to mechanical properties of the intracranial contents [17]. Finally, given the observed sexual dimorphism, this effect could be hypothesized to be mediated by previously observed effects of 17b-estradiol on human endothelial cell volume and elasticity [18].…”

NovelCOL2A1Variant (c.619G>A, p.Gly207Arg) Manifesting as a Phenotype Similar to Progressive Pseudorheumatoid Dysplasia and Spondyloepiphyseal Dysplasia, Stanescu Type

“…Type II collagen secretion into the extracellular matrix also decreases in human chondrocytes transfected with mutant as compared with wild-type WISP3 [Wang et al, 2013]. We hypothesize that the WISP3 variants found in PPRD and the COL2A1 variant described here both decrease type II collagen, potentially disrupting the extracellular matrix and common downstream signaling pathways [Barber et al, 2014].…”

Vitamin A in prevention and treatment of cancer

“…However, the incorporation of mineral micronutrients, zinc and selenium; and especially the vitamin supplements as well as their derivatives, and analogues have been found to bring some fruitful outcomes in cancer (Chen et al 2013;Cook-Mills et al 2013;Oliveira 2015). Being micronutrients and complexity in actions, the use of vitamins in cancer is not common (Barber et al 2014;Clamon 2015). However, in some non-clinical and clinical studies, the use (both individually and combindly) of vitamins for the prevention and treatment of cancers, is evident (Coulter et al 2006; Bjelakovic et al 2013a; Shukla et al 2014).…”