Effect of heparin-derived oligosaccharide on bFGFR1 and bFGFR2 in vascular smooth muscle cells.
Our purpose is to investigate the inhibitory effect and mechanisms of heparin-derived oligosaccharide (HDO) on proliferation of vascular smooth muscle cells (VSMCs) induced by basic fibroblast growth factor (bFGF). Proliferation of VSMCs was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide; cell cycle distribution was analyzed by flow cytometry; bFGF receptor 1 and receptor 2 (bFGFR1 and bFGFR2) messenger RNA (mRNA) expression levels were determined by reverse transcription-polymerase chain reaction; and its protein expression levels were detected by Western blotting and immunocytochemical methods. Results showed that HDO inhibited VSMC proliferation in a dose-dependent manner; HDO inhibited cells in G1 phase entering the S phase; HDO inhibited bFGFR1 and bFGFR2 mRNA expression levels. In addition, bFGFR1 and bFGFR2 protein expression levels were significantly inhibited by HDO dose dependently. These results imply that HDO can inhibit VSMC proliferation. The proliferation of bFGF-induced VSMCs by HDO is associated with the inhibition of bFGFR1 and bFGFR2 expression levels. This altered molecular signature may explain one mechanism of HDO-mediated inhibition of VSMC proliferation.
School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Danfeng
D
Yu
Xue
X
Rui
Shuying
S
He
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006493:Heparin / Q000494:pharmacology*; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D009844:Oligosaccharides / Q000494:pharmacology*; D051381:Rats; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000187:drug effects*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009844:Oligosaccharides; D006493:Heparin; C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2
basic fibroblast growth factor (bFGF); heparin-derived oligosaccharide (HDO); proliferation; vascular smooth muscle cell (VSMC)