Secreted modular calcium-binding is a laminin-binding matricellular protein belonging to the SPARC (osteonectin/BM-40) protein family that is expressed mainly in organ basement membranes and is a bone morphogenetic protein (BMP) antagonist. Given that (1) matricellular proteins are involved in tissue renewal and (2) the role of BMP in angiogenesis, the aim of this study was to determine whether SMOC-1 is expressed in cells (endothelial cells and monocytes) that influence angiogenesis and vascular repair, and if so to determine the signalling pathways affected.

SMOC-1 was expressed by macrophages and endothelial cells and its expression was regulated by inflammatory cytokines (interleukin-1b, transforming growth factor 1b, TGF-1 b and tumor necrosis factor 1a), anti-inflammatory lipids (nitro-oleic and nitro-linoleic acid), Krüppel like factor 2 (KLF2) and shear stress. Functionally, the presence of SMOC-1 in an endothelial cell-derived extracellular matrix (ECM) potentiated the migration, but prevented adhesion of monocytes (THP-1 cells) and endothelial cells. Furthermore, the absence of SMOC-1 lead to an impaired endothelial cell tube formationin vitro.In vivocell infiltration (of CD45+ cells) into Matrigel plugs was increased after 3 days in the presence of SMOC-1 and showed more prominent angiogenesis after another 7 days. Mechanistically, the co-expression of human SMOC-1 attenuated a TGF-1 b as well as BMP reporter gene construct in human embryonic kidney cells.

Together, this implies that SMOC-1 is a critical regulator for angiogenesis and tissue repair via its antagonism of TGF-1 b/BMP.