Intrauterine Growth Restriction‐Associated Increase in Lung Elastin is Due to Protein Deficiency

Abstract

ObjectivesTo determine 1) if increased lung elastin in intrauterine growth restricted (IUGR) infant is due to altered alveolar interstitial fibroblast (AIF) differentiation and 2) the specific nutrient deficiency that leads to increased elastin gene expression in the IUGR infant lung.MethodsPregnant rat dams were fed ad lib or on 50% food‐restricted diet. The pups were killed at 9 months and lungs were examined for elastin gene expression (RT‐PCR and Western blotting). Primary rat lung fibroblasts were cultured in DMEM ± fetal bovine serum (FBS), Vitamin D (VD), arachidonic acid (ARA) +doxohexanoic acid (DHA), or bovine serum albumin (BSA)‐ then the expression of elastin and activation of mTOR signaling were examined.ResultsWith food restriction there was a significant increase in elastin gene expression. Culturing primary AIFs without FBS significantly increased the expression and protein levels of various elastin‐related genes, accompanied by mTOR activation. FBS‐restriction associated increase in elastin expression and mTOR activation were only partially blocked by VD and ARA+DHA, but completely blocked with BSA.ConclusionsElastin expression is significantly increased in the lungs of IUGR offspring; this increase is largely due to protein deficiency; and AIF mTOR signaling plays an important role in increased elastin levels in the IUGR offspring lung. (Grant: NIH (HD‐58948).