title: The regulator of G-protein signaling 18 regulates platelet aggregation, hemostasis and thrombosis.
abstract: Regulators of G protein signaling (RGS) proteins are known to interact with and negatively regulate/turn-off G protein activation. RGS18 is identified as an R4 subfamily member of this family with specific expression in hematopoietic progenitors, myeloerythroid cells, megakaryocytes and platelets. Studies focused on understanding its function in platelet biology have been limited, in part, due to lack of pharmacological inhibitors. Thus, the present study investigated the function of RGS18 in platelets, using the RGS18 knockout mouse model (RGS18(-/-)). We identified phenotypic differences between RGS18(-/-) and wild-type (WT) mice, and show that RGS18 plays a significant role in hemostasis and thrombosis. Hence, RGS18 deficiency markedly shortened bleeding as well as occlusion times (in vivo). Furthermore, RGS18(-/-) platelets displayed hyper-responsiveness with regards to agonist induced aggregation (in vitro). This gain of function phenotype may serve as the mechanism or explain, at least in part, the enhanced hemostasis and thrombosis phenotype observed in the RGS18 deletion mice. Collectively, our findings provide valuable insight and highlight a critical and direct role for RGS18 in modulating platelet function.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Fatima Z
authors.initials: FZ
authors.lastname: Alshbool
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Zubair A
authors.initials: ZA
authors.lastname: Karim
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Hari Priya
authors.initials: HP
authors.lastname: Vemana
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Conlon
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Olivia A
authors.initials: OA
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA. Electronic address: fkhasawneh@westernu.edu.
authors.forename: Fadi T
authors.initials: FT
authors.lastname: Khasawneh
mesh_terms: D000818:Animals; D006487:Hemostasis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010974:Platelet Aggregation / Q000502:physiology*; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*; D013927:Thrombosis / Q000503:physiopathology*
chemical_list: D020710:RGS Proteins; C422991:Rgs18 protein, mouse
keywords: Hemostasis; Platelets; Regulator of G-protein signaling 18; Regulators of G-protein signaling; Signal transduction; Thrombosis