Alterations of peroxisome proliferator-activated receptor γ and monocyte chemoattractant protein 1 gene expression in the nitrofen-induced hypoplastic lung

Background/Purpose: Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a key role in normal lung development. Peroxisome proliferator-activated receptor gamma messenger RNA ( mRNA) is detectable at 18 days of gestation in fetal rat lungs, and levels peak just before birth. Peroxisome proliferator-activated receptor gamma agonists are reported to stimulate lung development, whereas inhibition of PPAR gamma disrupts postnatal lung maturation. Monocyte chemoattractant protein 1 ( MCP-1),which is inhibited by PPAR gamma, is reported to disrupt late lung morphogenesis. This study was designed to investigate the hypothesis that PPAR gamma expression is downregulated and that MCP-1 expression is upregulated during the late stages of lung development in nitrofen-induced hypoplastic lungs. Methods: Pregnant rats were treated with nitrofen or vehicle on D9. RNA was extracted from fetal lungs ( D18 and D21), and relative mRNA expression levels of PPAR gamma and MCP-1 were determined by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression/distribution of PPAR gamma and MCP-1. Results: Relative mRNA expression levels of PPAR gamma were significantly downregulated in the nitrofen group compared with controls on D21, whereas MCP-1 levels were upregulated. Immunohistochemical study showed markedly decreased PPAR gamma and increased MCP-1 immunoreactivity in the nitrofen-induced hypoplastic lungs compared with controls on gestational day 21. Conclusion: Altered pulmonary gene expression of PPAR gamma and MCP-1 during late gestation may impair lung development and maturation, contributing to pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia model. (c) 2012 Elsevier Inc. All rights reserved.