Abstract
Objectives:Lysophosphatidic acid(LPA)is a new class lipid mediator and exerts varied physiological and pathological functions through the binding to cell- membrane specific receptors. A secreting protein, autotaxin(ATX)is a key enzyme to determine local LPA production.We reported that placental ATX mRNA amount of the women with pregnancy induced hypertension(PIH) were significantly lower than that of normal women. Impaired implantation was reported in mice deficient in LPAR3, one of LPA receptors, suggesting the critical role of this pathway in reproduction. We aimed to explore the regulatory role of trophoblast cell function by ATX-LPA-LPAR3 pathway and its association with the pathology of PIH.Methods:We analyzed the local expression of ATX and LPAR3 in human placenta using immunohistochemistry. Next, we transfected LPAR3 gene to HTR-8/SVneo, a trophoblastic cell line, and stimulated it with the specific agonist of LPAR3. Real-time PCR was conducted to examined the impact of the stimulation on the expression level of angiogenic factors in LPAR3-transfected cells.All placental samples and the experiments were conducted under the approval of the ethical committee in our facility.Results:ATX-specific staining is confirmed in all types of trophoblasts. The expression of LPAR3 was restricted to differentiated trophoblasts including syncytiotrophoblast and extra-villous trophoblasts.LPAR3-transfected HTR-8/SVneo enhanced cyclooxygenase-2(COX-2), interleukin-8(IL-8), and vascular endotherial growth factor(VEGF)expression remarkably upon the stimulation with a specific agonist to LPAR3.Conclusion:Our findings revealed that ATX-LPA-LPAR3 pathway regulates the expression of angiogenic factors in trophoblasts. Reduced ATX production occuring in preeclamptic placentas might diminished the angiogenic property in trophoblasts, consequently leading to aberrant placentation.
