Effects of PDGF-C and PDGF-D on monocyte migration and MMP-2 and MMP-9 expression.
OBJECTIVE
Atherosclerosis is a chronic inflammatory process involving the activity of several cytokines and growth factors. Platelet-derived growth factor-A (PDGF-A) and PDGF-B are important mitogens and chemoattractants for monocytes as well as smooth muscle cells. We sought to identify the role of PDGF-C and PDGF-D, two new members of the PDGF family, in monocyte migration and differentiation. We also assessed their effects in regulating matrix metalloproteinase-2 (MMP-2) and MMP-9, which are important for cell migration.


RESULTS
PDGF-C and PDGF-D were expressed in macrophages, smooth muscle cells, and endothelial cells in human atherosclerotic plaques, as shown by immunohistochemical analysis. PDGF-C and PDGF-D mRNA and protein expression was induced after differentiation of THP-1 monocytes to macrophages, and both PDGF-C and PDGF-D induced MMP-9 mRNA expression in a concentration-dependent manner. Treatment of cells with PDGF-C or PDGF-D enhanced the secretion of MMP-2 and MMP-9 in a cell-dependent manner. In a migration assay using a Boyden chamber with 8 microm pore size, PDGF-C and PDGF-D attracted THP-1 monocytes in a concentration-dependent manner.


CONCLUSIONS
Our data suggest that PDGF-C and PDGF-D, like PDGF-A and PDGF-B, play important roles in atherosclerosis by stimulating MMP activity and influencing monocyte migration.
Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Stockholm, Sweden. Dick.Wagsater@ki.se
Dick
D
Wågsäter
Chaoyong
C
Zhu
Hanna M
HM
Björck
Per
P
Eriksson
D019898:Autocrine Communication / Q000502:physiology; D002340:Carotid Artery Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007938:Leukemia; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism
D016207:Cytokines; D008222:Lymphokines; C427493:PDGFD protein, human; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C411423:platelet-derived growth factor C; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9