Effects of Retinol Deficiency and Hyperoxia on Collagen Gene Expression in Rat Lung

Abstract

Exposure to hyperoxia results in lung injury and a decrease in lung collagen. Retinol is known to influence collagen gene expression, and retinol deficiency has been shown to potentiate hyperoxic lung injury. To investigate, the combined effects of retinol deficiency and hyperoxia on lung collagen expression, retinol-deficient rats were exposed to acute hyperoxia, and expression of the alpha-1 chains of type I procollagen [proα 1(I)] and type III procollagen [proα 1(III)] were determined using Northern hybridization analyses and immunohistochemical staining. Hyperoxia alone reduced proα 1(I) mRNA by 60 ± 4% (p < .05) and proα 1 (III) mRNA by 30 ± 5% (p <.05), and retinol deficiency alone reduced proα 1(I) mRNA abundance by 49 ± 8.8% (p < .05) and proα 1(III) mRNA abundance by 14 ± 7.5% (p = not significant), respectively. Retinol deficiency plus hyperoxia did not cause any further reduction in procollagen mRNA than that seen with oxygen exposure alone. Immunohistochemical staining demonstrated decreased staining for type I collagen in retinol-deficient animals. Hyperoxic exposure resulted in decreased connective tissue staining and increased alveolar wall staining for type I collagen. Retinol deficiency and hyperoxia together resulted in a marked increase in alveolar exudates staining for type I collagen. No changes in type III collagen staining were seen. These findings demonstrate that while retinol deficiency does not potentiate hyperoxia-induced reductions in procollagen mRNA, it is associated with alterations in collagen staining in distal lung and immunohistologic evidence of collagen fragments in alveolar exudates.