title: Lysophosphatidic Acid (LPA) Receptor 3-Mediated LPA Signal Transduction Pathways: A Possible Relationship with Early Development of Peri-Implantation Porcine Conceptus.
abstract: Lysophosphatidic acid (LPA) is a phospholipid with a variety of fatty acyl groups that mediates diverse biological effects on various types of cells through specific G protein-coupled receptors. LPA appears to play a significant role in many reproductive processes, including luteolysis, implantation, and placentation. Our previous study in pigs demonstrated that LPA and the LPA receptor system are present at the maternal-conceptus interface and that LPA increases uterine endometrial expression of prostaglandin-endoperoxide synthase 2 (PTGS2) through LPA receptor 3 (LPAR3). However, the role of LPA in conceptuses during early pregnancy has not been determined. Therefore, this study examined the effects of LPA in cell proliferation, migration, and activation of the intracellular signaling pathway in porcine conceptuses by using an established porcine trophectoderm (pTr) cell line isolated from Day 12 conceptuses. All examined LPA species with various fatty acid lengths increased proliferation and migration of pTr cells as the dosage increased. Immunoblot analyses found that LPA activated intracellular signaling molecules, extracellular signal-regulated kinase 1/2 (ERK1/2), ribosomal protein S6 kinase 90 kDa (P90RSK), ribosomal protein S6 (RPS6), and P38 in pTr cells. Furthermore, LPA increased expression of PTGS2 and urokinase-type plasminogen activator (PLAU), and the LPA-induced increases in PTGS2 and PLAU expression were inhibited by LPAR3 siRNA. Collectively, these results showed that LPA promotes proliferation, migration, and differentiation of pTr cells by activating the ERK1/2-P90RSK-RPS6 and P38 pathways, indicating that the LPA-LPAR3 system may be involved in the development of trophoblast during early pregnancy in pigs.
authors.affiliation: Department of Animal Resources Science, Dankook University, Cheonan, Republic of Korea.
authors.forename: Wooyoung
authors.initials: W
authors.lastname: Jeong
authors.affiliation: Division of Biological Science and Technology, Yonsei University, Wonju, Republic of Korea.
authors.forename: Heewon
authors.initials: H
authors.lastname: Seo
authors.affiliation: Department of Animal Resources Science, Dankook University, Cheonan, Republic of Korea.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Sung
authors.affiliation: Division of Biological Science and Technology, Yonsei University, Wonju, Republic of Korea hka@yonsei.ac.kr.
authors.forename: Hakhyun
authors.initials: H
authors.lastname: Ka
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea ghsong@korea.ac.kr.
authors.forename: Gwonhwa
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Animal Resources Science, Dankook University, Cheonan, Republic of Korea jinyoungkim@dankook.ac.kr.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004475:Ectoderm / Q000187:drug effects / Q000378:metabolism; D010064:Embryo Implantation / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D011247:Pregnancy; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D013552:Swine / Q000196:embryology*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid
keywords: conceptus; lysophosphatidic acid; migration; pig; proliferation