Expression of autotaxin and lysophosphatidic acid receptors 1 and 3 in the developing rat lung and in response to hyperoxia.

We sought to evaluate lysophosphatidic acid (LPA) signaling improvement in lung development by assessing the expression of autotaxin and LPA receptor 1 and 3 (LPAR1 and LPAR3) in the neonatal rat lung during normal perinatal development and in response to hyperoxia. In the developmental study, rats were sacrificed on days 17, 19, and 21 of gestation; on postnatal days 1, 4, and 7; and at adulthood (postnatal 9 weeks). In the hyperoxia study, 42 postnatal 4-day-old rat pups were divided into seven groups and exposed to either 85% O2 for 24, 72, or 120 h or room air for 0, 24, 72, or 120 h. The rats were then euthanized after 0, 24, 72, and 120 h of exposure. Immunofluorescence demonstrated that autotaxin, LPAR1, and LPAR3 proteins were broadly colocalized in airway epithelial cells, but mainly distributed in vascular endothelial and mesenchymal cells during the first postnatal week. The expression of autotaxin, LPAR1, and LPAR3 were increased during late gestation and then decreased after birth. Autotaxin expression and enzymatic activity were significantly increased at 72 and 120 h after exposure to hyperoxia. LPAR1 and LPAR3 expression was also increased after 120 h of hyperoxic exposure. These findings suggest that LPA-associated molecules were upregulated at birth and induced by hyperoxia in the developing rat lung. Therefore, the LPA pathway may be involved in normal lung development, including vascular development, as well as wound-healing processes of injured neonatal lung tissue, which is at risk of neonatal hyperoxic acute lung injury.