Nathan Lee | PubMed Health

PubMed2005

ADAMTS1 proteinase is up-regulated in wounded skin and regulates migration of fibroblasts and endothelial cells.

The metalloproteinase ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs) is induced under inflammatory conditions, and it is also a potent inhibitor of angiogenesis. Due to these properties, we speculated about the role of ADAMTS1 in cutaneous wound repair. Here we have shown up-regulation of ADAMTS1 expression in wounds of normal and particularly of healing-impaired genetically diabetic mice. Immunofluorescence staining identified macrophages as the source of ADAMTS1 in early wounds, whereas keratinocytes and fibroblasts produce this protein at later stages of wound healing. The distribution of ADAMTS1 in the normal and wounded epidermis, its regulation in cultured keratinocytes, as well as the skin phenotype of ADAMTS1 knock-out mice suggests a role of this metalloproteinase in keratinocyte differentiation. Furthermore, we provide evidence for a novel dual function of ADAMTS1 in fibroblast migration; although low concentrations of this protein stimulate fibroblast migration via its proteolytic activity, high concentrations inhibit this process because of binding to fibroblast growth factor-2 and subsequent inhibition of its promotogenic activity. Similar effects were also observed with endothelial cells. Taken together, our results suggest a role of ADAMTS1 in keratinocyte differentiation and migration of fibroblasts and endothelial cells in healing skin wounds.

ADAM Proteins↗

PubMed2004

Thrombospondin modules and angiogenesis.

Angiogenesis is a complex, multifactorial process that involves signals from endothelial cells and from the stoma. Extracellular matrix proteins participate in the modulation of growth factor response, contribute to the architecture of the vasculature and provide signals for the stabilization of mature capillary beds. The identification of the relevant extracellular matrix molecules and the characterization of their effects has been a central focus of research in vascular biology. Thrombospondin-1 is an extracellular glycoprotein first to be recognized as an inhibitor of angiogenesis more than a decade ago. Since then, much has been learned about its ability to regulate vascular growth in several angiogenesis models, functional domains have been identified, and mechanisms of action determined. This review summarizes current understanding on the effects of thrombospondin-1 and -2 during the process of angiogenesis. We will also extend our comments to ADAMTS1, a member of a relatively novel group of matrix metalloproteinases with thrombospondin repeats and shown to affect endothelial cell function and angiogenesis.

Animals↗