title: Platelet-activating factor (PAF) increase intracellular lipid accumulation by increasing both LDL and scavenger receptors in human mesangial cells.
abstract: Intra- and extracellular lipid accumulation and the production of inflammatory mediators by renal and accessory cells may play an important role in the initiation and progression of these lesions. Platelet activating factor (PAF) is a biologically active phospholipid that is produced by various cells upon activation by different stimuli. It has been suggested that PAF plays a role in atherogenesis, and several studies indicated its participation in the pathogenesis of renal diseases. The aim of this study is to investigate the role of PAF on intracellular lipid accumulation and gene regulation of lipoprotein receptors in human mesangial cells (HMCs). A human mesangial cell line (HMC) was used to study the effects of PAF on foam cell formation by Oil red O staining and on the expression of LDLr, SR-AI, and PAF-R mRNA using RT-PCR. Native LDL caused foam cell formation in HMC in the presence of PAF. PAF enhanced LDLr expression and overrode LDL receptor suppression induced by a high concentration of LDL. Moreover, it enhanced SR-AI expression. PAF also caused increase in PAF-R expression. The above data suggest that PAF enhances its own receptor expression and then increases lipid accumulation by dysregulating LDL receptor regulation and inducing scavenger receptor expression in HMCs. These results suggest that PAF has a potential role in lipid mediated renal injury.
authors.affiliation: Faculty of Chemistry, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fragopoulou
authors.forename: Christos
authors.initials: C
authors.lastname: Iatrou
authors.forename: Smaragdi
authors.initials: S
authors.lastname: Antonopoulou
authors.forename: Xiong-Zhong
authors.initials: XZ
authors.lastname: Ruan
authors.forename: Ray L
authors.initials: RL
authors.lastname: Fernando
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Powis
authors.forename: John F
authors.initials: JF
authors.lastname: Moorhead
authors.forename: Zac
authors.initials: Z
authors.lastname: Varghese
mesh_terms: D002461:Cell Line, Transformed; D008078:Cholesterol, LDL / Q000493:pharmacokinetics*; D005487:Foam Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D014316:Tritium
chemical_list: D008078:Cholesterol, LDL; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011973:Receptors, LDL; D051117:Scavenger Receptors, Class A; C039351:platelet activating factor receptor; D014316:Tritium