title: Decorin mimic regulates platelet-derived growth factor and interferon-γ stimulation of vascular smooth muscle cells.
abstract: Following balloon injury, smooth muscle cells (SMCs) serve as targets for many of the pro-inflammatory and pro-fibrotic factors, including platelet-derived growth factor (PDGF) and interferon-γ (IFN-γ) released from activated inflammatory cells and platelets. Previously, our lab designed a mimic of the proteoglycan decorin, termed DS-SILY20, that suppressed vascular SMC proliferation, migration, and protein synthesis in vitro, and injured vessels treated with DS-SILY20 demonstrated reduced hyperplasia in vivo. Here we characterize the effects of DS-SILY20 on modulating PDGF and IFN-γ stimulation in both proliferative and quiescent human SMCs to further evaluate the potential impact of DS-SILY20-SMC interaction on restenosis. Nanomolar dissociation constants were observed between DS-SILY20 and both PDGF and IFN-γ. PDGF significantly increased migration, proliferation, and protein and cytokine expression, as well as increased ERK-1/2 and p38 MAPK phosphorylation in both quiescent and proliferative cultures. However, DS-SILY20 inhibited these increases, presumably through sequestration of the PDGF. Consistent with the complex responses seen with IFN-γ in SMC physiology in the literature, the response of SMC cultures to IFN-γ was variable and complex. However, where increased activity was seen with IFN-γ, DS-SILY20 attenuated this activity. Overall, the results suggest that DS-SILY20 would be an ideal alternative to traditional therapeutics used and may be an effective therapy for the prevention of intimal hyperplasia after balloon angioplasty.
authors.affiliation: Weldon School of Biomedical Engineering Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Scott
authors.forename: Alyssa
authors.initials: A
authors.lastname: Panitch
mesh_terms: D000595:Amino Acid Sequence; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D058575:Decorin / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology
chemical_list: C546878:DCN protein, human; D058575:Decorin; D010982:Platelet-Derived Growth Factor; D007371:Interferon-gamma