The synthesis of a family of structurally related proteoglycans in fibroblasts is differently regulated by TFG-beta.
Fibroblasts synthesize a variety of proteoglycans among which is a family of structurally related small proteoglycans, i.e. PG-S1 (biglycan) and PG-S2 (decorin). Fibromodulin, which is present in some tissues as a keratan sulfate proteoglycan, also belongs to this family. We have used primary fibroblasts from fetal skin and bovine sclera in culture to study the metabolism of proteoglycans. In particular the regulatory effect of transforming growth factor-beta (TGF-beta), interleukin-1 (IL-1) platelet-derived growth factor (PDGF) and dexamethasone was determined by studies of mRNA levels for these structurally related proteoglycans. Furthermore the synthesis and secretion of these macromolecules was studied using radioactive precursors. TGF-beta induced a 3-fold increase of mRNA for PG-S1, collagen I and III in both types of fibroblasts. mRNA for PG-S2 increased only slightly (1.7-fold) in human skin fibroblasts; while no effect was noticed in sclera fibroblasts. The expression of fibromodulin mRNA was not effected in any of the cells investigated. IL-1, PDGF and dexamethasone had no significant effects on the levels of proteoglycan and collagen mRNA, respectively. Synthesis and secretion of PG-S1, -S2 and fibromodulin wa studied by labeling with [3H]-leucine and [35S]-sulfate. Final separation of PG-S1 and -S2 was achieved by hydrophobic interaction chromatography. TGF-beta induced a 3- to 6-fold increase of [3H]- and [35S]-labeled PG-S1; while PG-S2 only increased 1.3- to 1.4-fold in both types of fibroblasts. No effect on synthesis and secretion of immunoprecipitated fibromodulin was noted.(ABSTRACT TRUNCATED AT 250 WORDS)
Westergren-Thorsson
G
G
Department of Physiological Chemistry, University of Lund, Sweden.
Antonsson
P
P
Malmström
A
A
Heinegård
D
D
Oldberg
A
A
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics; D002417:Cattle; D002478:Cells, Cultured; D002850:Chromatography, Gel; D003094:Collagen / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004622:Embryo, Mammalian; D016326:Extracellular Matrix Proteins; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D000071235:Fibromodulin; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000302:isolation & purification; D006801:Humans; D011509:Proteoglycans / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012590:Sclera / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013552:Swine; D016212:Transforming Growth Factor beta / Q000302:isolation & purification / Q000494:pharmacology*
D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D006025:Glycosaminoglycans; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000071235:Fibromodulin; D003907:Dexamethasone; D003094:Collagen