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-1alpha, IL-1beta and
TNF-alpha, did not change, but
myeloperoxidase and
TGF-beta1 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-beta1 and reverted by
retinoic acid. These alterations could contribute to the impairment of lung function and predispose to
pulmonary disease.