A role for GPR55 in human placental venous endothelial cells
- 292 Downloads
Endocannabinoids and their G protein-coupled receptors have been suggested to play a key role in human pregnancy, by regulating important aspects such as implantation, decidualization, placentation and labor. G protein-coupled receptor 55 (GPR55) was previously postulated to be another cannabinoid receptor, since specific cannabinoids were shown to act independently of the classical cannabinoid receptors CB1 or CB2. Current knowledge about GPR55 expression and function in human placenta is very limited and motivated us to evaluate human placental GPR55 expression in relation to other human peripheral tissues and to analyze spatiotemporal GPR55 expression in human placenta. Gene expression analysis revealed low GPR55 levels in human placenta, when compared to spleen and lung, the organs showing highest GPR55 expression. Moreover, expression analysis showed 5.8 fold increased placental GPR55 expression at term compared to first trimester. Immunohistochemistry located GPR55 solely at the fetal endothelium of first trimester and term placentas. qPCR and immunocytochemistry consistently confirmed GPR55 expression in isolated primary placental arterial and venous endothelial cells. Incubation with L-α-lysophosphatidylinositol (LPI), the specific and functional ligand for GPR55, at a concentration of 1 µM, significantly enhanced migration of venous, but not arterial endothelial cells. LPI-enhanced migration was inhibited by the GPR55 antagonist O-1918, suggesting a role of the LPI-GPR55 axis in placental venous endothelium function.
KeywordsHuman placenta Primary placental endothelial cells Cannabinoid receptors G protein-coupled receptor 55
The authors thank Bettina Amtmann and Petra Wagner for recruiting placental tissue samples for this study. Moreover, the authors are indebted to Heidi Miedl and Monika Sundl for their cell isolation, cell culture work and assistance with immunohistochemistry. First-trimester placental tissues were provided by Dr. Andreas Glasner. M. Gauster is supported by the Austrian Science Fund (FWF): P23859-B19.
Conflict of interest
The authors declare they have no conflict of interest.
- AlSuleimani YM, Hiley CR (2015) The GPR55 agonist lysophosphatidylinositol mediates vasorelaxation of the rat mesenteric resistance artery and induces calcium release in rat mesenteric artery endothelial cells. Br J PharmacolGoogle Scholar
- Di Francesco A, Falconi A, Di Germanio C, Micioni Di Bonaventura MV, Costa A, Caramuta S, Del Carlo M, Compagnone D, Dainese E, Cifani C, Maccarrone M, D’Addario C (2014) Extravirgin olive oil up-regulates CB tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms. J Nutr BiochemGoogle Scholar
- Ford LA, Roelofs AJ, Anavi-Goffer S, Mowat L, Simpson DG, Irving AJ, Rogers MJ, Rajnicek AM, Ross RA (2010) A role for L-alpha-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells. Br J Pharmacol 160:762–771PubMedCentralPubMedCrossRefGoogle Scholar
- Kotsikorou E, Madrigal KE, Hurst DP, Sharir H, Lynch DL, Heynen-Genel S, Milan LB, Chung TD, Seltzman HH, Bai Y, Caron MG, Barak L, Abood ME, Reggio PH (2011) Identification of the GPR55 agonist binding site using a novel set of high-potency GPR55 selective ligands. Biochemistry 50:5633–5647PubMedCentralPubMedCrossRefGoogle Scholar
- Lang I, Schweizer A, Hiden U, Ghaffari-Tabrizi N, Hagendorfer G, Bilban M, Pabst MA, Korgun ET, Dohr G, Desoye G (2008) Human fetal placental endothelial cells have a mature arterial and a juvenile venous phenotype with adipogenic and osteogenic differentiation potential. Differentiation 76:1031–1043PubMedCrossRefGoogle Scholar
- Moreno-Navarrete JM, Catalan V, Whyte L, Diaz-Arteaga A, Vazquez-Martinez R, Rotellar F, Guzman R, Gomez-Ambrosi J, Pulido MR, Russell WR, Imbernon M, Ross RA, Malagon MM, Dieguez C, Fernandez-Real JM, Fruhbeck G, Nogueiras R (2012) The L-alpha-lysophosphatidylinositol/GPR55 system and its potential role in human obesity. Diabetes 61:281–291PubMedCentralPubMedCrossRefGoogle Scholar
- Sawzdargo M, Nguyen T, Lee DK, Lynch KR, Cheng R, Heng HH, George SR, O’Dowd BF (1999) Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Brain Res Mol Brain Res 64:193–198PubMedCrossRefGoogle Scholar
- Waldeck-Weiermair M, Zoratti C, Osibow K, Balenga N, Goessnitzer E, Waldhoer M, Malli R, Graier WF (2008) Integrin clustering enables anandamide-induced Ca2 + signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression. J Cell Sci 121:1704–1717PubMedCentralPubMedCrossRefGoogle Scholar
- Wilhelmsen K, Khakpour S, Tran A, Sheehan K, Schumacher M, Xu F, Hellman J (2014) The endocannabinoid/endovanilloid N-arachidonoyl dopamine (NADA) and synthetic cannabinoid WIN55,212-2 abate the inflammatory activation of human endothelial cells. J Biol Chem 289:13079–13100PubMedCentralPubMedCrossRefGoogle Scholar