State Key Laboratory of Cardiovascular Disease, Fuwai Hospital & Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China.
Mol Biol Rep. 2012 Sep;39(9):9075-84. doi: 10.1007/s11033-012-1778-6. Epub 2012 Jun 28.
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.
溶血磷脂（LPs）是调节多种生理和病理过程的小信号脂质，通过 G 蛋白偶联受体发挥作用。为了研究 LP 信号在心脏器官发生和成熟中的功能，我们测量了从胚胎期 19.5 天（E19.5d）到出生后第 12 周（P12w）的大鼠心脏中 10 种已确认的 LP 受体（Lpar1-5 和 S1pr1-5）的表达。Lpar3 mRNA 的表达在出生后第 1 天（P1d）达到峰值，比成人表达高出 37 倍，而 Lpar1 和 Lpar4 的表达水平在 P1d 后显著增加，在 P7d 时达到成人表达的 19 倍和 48 倍。所有三种受体 mRNA 的表达水平在 P21d 时显著降低，此后一直保持较低水平。相应的受体蛋白的表达也在出生后早期达到峰值，但从 P14d 到 P12w 的下降幅度小于 mRNA 表达。相比之下，S1pr1 和 S1pr3 表现出更为渐进的发育变化。尽管早期表达高于成熟表达（3-6 倍），但这些受体在 P12w 时仍有强烈表达。在所有发育阶段，其他检查的亚型，Lpar2、Lpar5、S1pr4 和 S1pr5 的表达水平都非常低。在发育中的心脏（P1d）内分析受体分布显示，Lpar1、Lpar3 和 Lpar4 在心腔的所有四个腔室中的心肌中表达，但不在瓣膜中表达，而 Lpar3 也在主动脉和冠状动脉中独特表达。Western blot 显示，Lpar1、Lpar3 和 Lpar4 蛋白表达的发育变化与 β-肌动蛋白和 β-微管蛋白表达的变化相匹配。从 P1d 到 P7d，Lpar1 和 Lpar4 受体的增加与心肌生长和功能成熟的快速阶段相对应。此外，在产前晚期大鼠心脏中 Lpar1、Lpar3 和 Lpar4 的相对高表达表明，这些 LPA 受体也可能有助于器官发生。Lpar3 和 Lpar4 表达的增加伴随着细胞骨架蛋白表达的增加，进一步表明 LPA 信号在心脏发育过程中细胞骨架重塑中的可能作用。
