|INTRAUTERINE GROWTH RESTRICTION LEADS TO PROFIBROTIC LESIONS IN THE RAT LUNG|
Christian Plank1, Andrea Hartner1, Kerstin Amann2, Wolfgang Rascher1, Jörg
1 Department of Pediatrics and Adolescents, University Erlangen-Nuremberg, Erlangen, Germany
2 Department of Pathology, University Erlangen-Nuremberg, Erlangen, Germany
Aim of the study: Observational studies in children suggest that intrauterine growth restriction (IUGR) may be associated with a higher risk to develop bronchopulmonary dysplasia after preterm birth as well as a higher risk for the development of asthma in later life after term birth. Therefore, we tested the hypothesis that IUGR leads to a differential expression of profibrotic and inflammatory markers in the lungs of former IUGR animals at different ages.
Methods: IUGR was induced in Wistar rats by isocaloric protein restriction (low protein diet with 8% casein content versus normal protein diet with 17% casein content) in pregnant dams. Directly after birth, litter size was reduced to 6 male neonates in low protein animals (LP) and normal protein animals (NP). Rats were sacrificed directly after birth, at day 42, day 70 and day 120. Parts of the right inferior lung lobe were removed and immediately snap-frozen to investigate the mRNA-expression of profibrotic and inflammatory markers via real-time PCR.
Results: In neonatal lungs of IUGR animals we observed a significantly decreased expression of profibrotic markers (OPN, PAI1, TGFß1). Later in life, expression of profibrotic and inflammatory markers like TGFß1, MCP1 and PAI1 as well as TIMP1 and TIMP2 and cytokines like Interleukin 6 and Interleukin 13 are significantly increased in the lung tissue of former IUGR animals.
Conclusion: We therefore conclude that IUGR leads to altered inflammatory and profibrotic processes in the rat lung. This might be one explanation for a reduced airway function after IUGR as well as for a higher susceptibility for asthmatic and allergic diseases after IUGR.