Developmental changes in lysophospholipid receptor expression in rodent heart from near-term fetus to adult

Lysophospholipids (LPs) are small signaling lipids that regulate diverse physiological and pathological processes through G protein-coupled receptors. To investigate the function of LP signaling in heart organogenesis and maturation, we measured the expression of 10 confirmed LP receptors (Lpar1-5 and S1pr1-5) in rat heart from embryonic day 19.5 (E19.5d) to postnatal week 12 (P12w). The expression of Lpar3 mRNA peaked at 37-fold higher than adult expression at P1d, while the expression levels of Lpar1 and Lpar4 increased markedly after P1d and peaked at 19- and 48-folds of adult expression on P7d. The expression levels of all three receptor mRNAs were significantly reduced by P21d and remained low thereafter. Expression of the corresponding receptor proteins also peaked during the early postnatal period but the subsequent decline was less dramatic from P14d to P12w compared to mRNA expression. In contrast, S1pr1 and S1pr3 exhibited more gradual developmental changes. Although early expression was higher than mature expression (3- to 6-fold), these receptors were still strongly expressed at P12w. The other isotypes examined, Lpar2, Lpar5, S1pr4, and S1pr5, were very weakly expressed at all developmental stages. Analysis of receptor distribution within the developing heart (P1d) revealed that Lpar1, Lpar3, and Lpar4 were expressed in the myocardium of all four chambers but not in valves, while Lpar3 was also uniquely expressed in the aorta and coronary vessels. Western blots revealed that the developmental changes in Lpar1, Lpar3, and Lpar4 protein expression mirrored changes in β-actin and β-tubulin expression. The increase in Lpar1 and Lpar4 receptors from P1d to P7d corresponds to the period of rapid myocardial growth and functional maturation. Moreover, the relatively high expression of Lpar1, Lpar3, and Lpar4 in the late prenatal rat heart suggests that these LPA receptors may also contribute to organogenesis. The increase in Lpar3 and Lpar4 expression concomitant with rising expression of cytoskeleton proteins further suggests a possible role for LPA signaling in cytoskeletal remodeling during cardiac development.