title: Serglycin in Quiescent and Proliferating Primary Endothelial Cells.
abstract: Proteoglycans are fundamental components of the endothelial barrier, but the functions of the proteoglycan serglycin in endothelium are less described. Our aim was to describe the roles of serglycin in processes relevant for endothelial dysfunction. Primary human umbilical vein endothelial cells (HUVEC) were cultured in vitro and the expression of proteoglycans was investigated. Dense cell cultures representing the quiescent endothelium coating the vasculature was compared to sparse activated cell cultures, relevant for diabetes, cancer and cardiovascular disease. Secretion of 35S- proteoglycans increased in sparse cultures, and we showed that serglycin is a major component of the cell-density sensitive proteoglycan population. In contrast to the other proteoglycans, serglycin expression and secretion was higher in proliferating compared to quiescent HUVEC. RNAi silencing of serglycin inhibited proliferation and wound healing, and serglycin expression and secretion was augmented by hypoxia, mechanical strain and IL-1β induced inflammation. Notably, the secretion of the angiogenic chemokine CCL2 resulting from IL-1β activation, was increased in serglycin knockdown cells, while angiopoietin was not affected. Both serglycin and CCL2 were secreted predominantly to the apical side of polarized HUVEC, and serglycin and CCL2 co-localized both in perinuclear areas and in vesicles. These results suggest functions for serglycin in endothelial cells trough interactions with partner molecules, in biological processes with relevance for diabetic complications, cardiovascular disease and cancer development.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Box 1046, Blindern, 0316 Oslo, Norway.|Section of Renal Diseases, Department of Organ Transplantation, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
authors.forename: Trine M
authors.initials: TM
authors.lastname: Reine
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Box 1046, Blindern, 0316 Oslo, Norway.
authors.forename: Tram T
authors.initials: TT
authors.lastname: Vuong
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.|Department of Emergency and Intensive Care, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Arkady
authors.initials: A
authors.lastname: Rutkovskiy
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Box 1046, Blindern, 0316 Oslo, Norway.
authors.forename: Astri J
authors.initials: AJ
authors.lastname: Meen
authors.affiliation: Department of Emergency and Intensive Care, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Jarle
authors.initials: J
authors.lastname: Vaage
authors.affiliation: Section of Renal Diseases, Department of Organ Transplantation, Oslo University Hospital-Rikshospitalet, Oslo, Norway.|Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Trond G
authors.initials: TG
authors.lastname: Jenssen
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Box 1046, Blindern, 0316 Oslo, Norway.
authors.forename: Svein O
authors.initials: SO
authors.lastname: Kolset
mesh_terms: D002450:Cell Communication; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D014945:Wound Healing
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508585:IL1B protein, human; D053583:Interleukin-1beta; D011509:Proteoglycans; D033921:Vesicular Transport Proteins; C075430:serglycin