Thromboxane stimulates synthesis of extracellular matrix proteins in vitro.
The vasoconstrictor eicosanoid thromboxane plays an important role in the pathogenesis of several renal diseases. As an autacoid, its local release alters blood flow and induces platelet aggregation. We report a direct stimulatory effect of thromboxane on extracellular matrix protein production and gene expression in vitro. Treatment of two cell types, differentiated mouse teratocarcinoma cells (F9+) and human glomerular mesangial cells, with two different thromboxane analogues resulted in increased production of components of the extracellular matrix including fibronectin and the basement membrane proteins laminin and type IV collagen. These responses to thromboxane were not the result of a mitogenic effect of thromboxane nor the result of an increase in total cellular protein. The increased production of extracellular matrix proteins was, at least in part, due to an increase in the steady-state level of mRNA for these genes. Furthermore, the effect of thromboxane was markedly inhibited by cotreatment with a thromboxane-receptor antagonist. These results suggest a new potential role for thromboxane as a mediator of the sclerotic and fibrotic responses to injury.
Bruggeman
L A
LA
Molecular Medicine Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Horigan
E A
EA
Horikoshi
S
S
Ray
P E
PE
Klotman
P E
PE
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000328:Adult; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005353:Fibronectins / Q000235:genetics; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007797:Laminin / Q000235:genetics; D051379:Mice; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D013724:Teratoma; D013931:Thromboxanes / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D001713:Biphenyl Compounds; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016326:Extracellular Matrix Proteins; D005231:Fatty Acids, Unsaturated; D005353:Fibronectins; D006538:Heptanoic Acids; D007797:Laminin; D011450:Prostaglandin Endoperoxides, Synthetic; D012333:RNA, Messenger; D013931:Thromboxanes; C061750:7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; C060013:vapiprost; D013936:Thymidine