title: Vitamin A deficiency disturbs collagen IV and laminin composition and decreases matrix metalloproteinase concentrations in rat lung. Partial reversibility by retinoic acid.
abstract: Vitamin A is essential for lung development and pulmonary cell differentiation. Its deficiency leads to altered lung structure and function and to basement membrane architecture and composition disturbances. Previously, we showed that lack of retinoids thickens the alveolar basement membrane and increases collagen IV, which are reversed by retinoic acid, the main biologically active vitamin A form. This study analyzed how vitamin A deficiency affects the subunit composition of collagen IV and laminin of lung basement membranes and pulmonary matrix metalloproteinase content, plus the recovering effect of all-trans-retinoic acid. Male weanling pups were fed a retinol-adequate/-deficient diet until 60 days old. A subgroup of vitamin-A-deficient pups received daily intraperitoneal all-trans-retinoic acid injections for 10 days. Collagen IV and laminin chain composition were modified in vitamin-A-deficient rats. The protein and mRNA contents of chains α1(IV), α3(IV) and α4(IV) increased; those of chains α2(IV) and α5(IV) remained unchanged; and the protein and mRNA contents of laminin chains α5, β1 and γ1 decreased. The mRNA of laminin chains α2 and α4 also decreased. Matrix metalloproteinases 2 and 9 decreased, but the tissue inhibitors of metalloproteinases 1 and 2 did not change. Treating vitamin-A-deficient rats with retinoic acid reversed all alterations, but laminin chains α2, α4 and α5 and matrix metalloproteinase 2 remained low. In conclusion, vitamin A deficiency alters the subunit composition of collagen IV and laminin and the lung's proteolytic potential, which are partly reverted by retinoic acid. These alterations could contribute to impaired lung function and predispose to pulmonary disease.
authors: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Valencia, Avda Vicent A. Estellés s/n, 46100-Burjassot, Valencia, Spain.
authors: Guillermo
authors: G
authors: Esteban-Pretel
authors: M Pilar
authors: MP
authors: Marín
authors: Jaime
authors: J
authors: Renau-Piqueras
authors: Yoshikazu
authors: Y
authors: Sado
authors: Teresa
authors: T
authors: Barber
authors: Joaquín
authors: J
authors: Timoneda
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000097:blood; D014802:Vitamin A Deficiency / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D024141:Collagen Type IV; D007797:Laminin; D019714:Tissue Inhibitor of Metalloproteinases; D014801:Vitamin A; D014212:Tretinoin; D020782:Matrix Metalloproteinases