Basic fibroblast growth factor decreases type V/XI collagen expression in cultured bovine aortic smooth muscle cells.
Vascular smooth muscle cells (SMCs), the major cellular constituent of an artery, synthesize the bulk of fibrillar collagens, including type V/XI, which regulates heterotypic collagen fibril assembly. Basic fibroblast growth factor (bFGF) is a heparin-binding polypeptide growth factor that has been implicated in important events during the development of atherosclerosis, such as early intimal SMC proliferation. Here we have investigated the effects of bFGF on aortic SMC expression of type V/XI collagen. Treatment of exponentially growing or serum-deprived subconfluent cultures of bovine aortic SMCs with bFGF decreased the steady-state levels of the mRNAs for collagen type V/XI, including alpha 1(V), alpha 2(V), and alpha 1(XI). The effect of bFGF was time dependent with a two- and a fourfold decrease in alpha 2(V) mRNA observed after treatment for 24 and 48 h, respectively. This decrease resulted from a drop in the rate of alpha 2(V) gene transcription; no change was observed in the stability of the alpha 2(V) mRNA. Furthermore, accumulation of collagen protein decreased upon bFGF treatment. As expected, treatment with bFGF increased the rate of proliferation of serum-deprived SMCs, as judged by DNA content in the cultures, thymidine incorporation, and steady-state mRNA levels of the S-phase-expressed histone H3.2. These results suggest that bFGF plays an important role in the regulation of collagen fibril structure, with potential implications for the development and organization of an atherosclerotic lesion.
Kypreos
K E
KE
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
Sonenshein
G E
GE
D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011347:Procollagen / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D011347:Procollagen; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D003094:Collagen