Volume 21, Issue 3 , Pages 227-236, March 2010
Vitamin A deficiency alters rat lung alveolar basement membrane Reversibility by retinoic acid☆
Abstract
Vitamin A is essential for lung development and pulmonary cell differentiation and its deficiency results in alterations of lung structure and function. Basement membranes (BMs) are also involved in those processes, and retinoic acid, the main biologically active form of vitamin A, influences the expression of extracellular matrix macromolecules. Therefore, we have analyzed the ultrastructure and collagen content of lung alveolar BM in growing rats deficient in vitamin A and the recovering effect of all-trans retinoic acid. Male weanling pups were fed a retinol-adequate or -deficient diet until they were 60 days old. A group of vitamin A-deficient pups were recovered by daily intraperitoneal injections of all-trans retinoic acid for 10 days. Alveolar BM in vitamin A-deficient rats doubled its thickness and contained irregularly scattered collagen fibrils. Immunocytochemistry revealed that these fibrils were composed of collagen I. Total content of both collagen I protein and its mRNA was greater in vitamin-deficient lungs. In agreement with the greater size of the BM the amount of collagen IV was also increased. Proinflammatory cytokines, IL-1α, IL-1β and TNF-α, did not change, but myeloperoxidase and TGF-β1 were increased. Treatment of vitamin A-deficient rats with retinoic acid reversed all the alterations, but the BM thickness recovered only partially. Retinoic acid recovering activity occurred in the presence of increasing oxidative stress. In conclusion, vitamin A deficiency results in alterations of the structure and composition of the alveolar BM which are probably mediated by TGF-β1 and reverted by retinoic acid. These alterations could contribute to the impairment of lung function and predispose to pulmonary disease.
Keywords: Vitamin A, Retinoic acid, Basement membrane, Collagen, Oxidative stress, TGF-β1
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☆ This work was supported by Fondo de Investigación Sanitaria (FIS 05/2534), Spain; Fondo Europeo de Desarrollo Regional, U. Europea; and Generalitat Valenciana (grant GV2004-B-172). Guillermo Esteban-Pretel was a recipient of a fellowship from Generalitat Valenciana.
PII: S0955-2863(08)00267-2
doi:10.1016/j.jnutbio.2008.12.007
© 2010 Elsevier Inc. All rights reserved.
Volume 21, Issue 3 , Pages 227-236, March 2010
