IUGR decreases elastin mRNA expression in the developing rat lung and alters elastin content and lung compliance in the mature rat lung

Abstract

Complications of intrauterine growth restriction (IUGR) include increased pulmonary morbidities and impaired alveolar development. Normal alveolar development depends upon elastin expression and processing, as well as the formation and deposition of elastic fibers. This is true of the human and rat. In this study, we hypothesized that uteroplacental insufficiency (UPI)-induced IUGR decreases mRNA levels of elastin and genes required for elastin fiber synthesis and assembly, at birth (prealveolarization) and postnatal day 7 (midalveolarization) in the rat. We further hypothesized that this would be accompanied by reduced elastic fiber deposition and increased static compliance at postnatal day 21 (mature lung). We used a well characterized rat model of IUGR to test these hypotheses. IUGR decreases mRNA transcript levels of genes essential for elastic fiber formation, including elastin, at birth and day 7. In the day 21 lung, IUGR decreases elastic fiber deposition and increases static lung compliance. We conclude that IUGR decreases mRNA transcript levels of elastic fiber synthesis genes, before and during alveolarization leading to a reduced elastic fiber density and increased static lung compliance in the mature lung. We speculate that the mechanism by which IUGR predisposes to pulmonary disease may be via decreased lung elastic fiber deposition.

Developmental regulation of inflammatory cytokine-mediated Stat3 signaling: the missing link between intrauterine growth restriction and pulmonary dysfunction?

“…Several studies indicate that a severely perturbed extracellular matrix (ECM) metabolism contributes to the impairment of lung function and suggest a regulatory effect of IUGR on the pulmonary structure and production of ECM components [9,11]. Both lung structure and function are already determined during early and late lung development [12,13].…”

“…For example, maturation of the surfactant system is controversially discussed: there are studies reporting a delayed maturation of the surfactant proteins subsequent to IUGR [14], whereas other groups either state no alterations [15,16] or increased maturation of the surfactant proteins after IUGR [17]. In line with this developmental deregulation, Joss-Moore et al recently suggested a pivotal role of ECM components such as elastic fibers in the pathomechanism of IUGR-associated lung disease [11]. Although several studies have investigated the synthesis of pulmonary ECM and impaired lung function associated with IUGR, the molecular mechanism linking perturbed ECM with IUGR remains largely unclear to date.…”

Distant effects of unilateral renal ischemia/reperfusion on contralateral kidney but not lung in rats: the roles of ROS and iNOS

“…The rat was disconnected from the ventilator and sequential 2 ml injections of air were delivered, with repeated measure of airway pressure at 5 sec after each injection until a final airway pressure of 30 cmH 2 O was reached. The rat was the re-connected to the ventilator for 30 sec, and the procedure repeated three times (Joss-Moore et al 2011). …”

IUGR increases chromatin-remodeling factor Brg1 expression and binding to GR exon 1.7 promoter in newborn male rat hippocampus

“…Surgical methods have been described previously (27,34). Briefly, on day 19.5 of gestation (term gestation in the rat is 21.5 days), pregnant rats were anesthetized with intraperitoneal xylazine (8 mg/kg) and ketamine (40 mg/kg), and both uterine arteries were ligated to induce IUGR in the pups.…”