Independent modulation of collagen fibrillogenesis by decorin and lumican.
The leucine-rich proteoglycans (also known as "small, leucine-rich proteoglycans," or SLRPs) lumican and decorin are thought to be involved in the regulation of collagen fibril assembly. Preparation of these proteoglycans in chemical amounts without exposure to denaturants has recently been achieved by infecting HT-1080 cells with vaccinia virus that contains an expression cassette for these molecules. Addition of lumican and decorin to a collagen fibrillogenesis assay based on turbidity demonstrated that lumican accelerated initial fibril formation while decorin retarded initial fibril formation. At the end of fibrillogenesis, both proteoglycans resulted in an overall reduced turbidity, suggesting that fibril diameter was lower. The presence of both proteoglycans had a synergistic effect, retarding fibril formation to a greater degree than either proteoglycan individually. Competitive binding studies showed that lumican did not compete for decorin-binding sites on collagen fibrils. Both proteoglycans increased the stability of fibrils to thermal denaturation to approximately the same degree. These studies show that lumican does not compete for decorin-binding sites on collagen, that decorin and lumican modulate collagen fibrillogenesis, and that, in the process, they also enhance collagen fibril stability.
Neame
P J
PJ
Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa 33620, USA. pneame@com1.med.usf.edu
Kay
C J
CJ
McQuillan
D J
DJ
Beales
M P
MP
Hassell
J R
JR
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002417:Cattle; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism / Q000494:pharmacology*; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism*; D058575:Decorin; D005109:Extracellular Matrix / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006801:Humans; D066298:In Vitro Techniques; D007632:Keratan Sulfate / Q000378:metabolism / Q000494:pharmacology*; D000071234:Lumican; D011489:Protein Denaturation / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604306:LUM protein, human; D000071234:Lumican; D011509:Proteoglycans; D011994:Recombinant Proteins; D003094:Collagen; D007632:Keratan Sulfate