Integrin-dependent Functions of the Angiogenic Inducer NOV (CCN3)

The novel angiogenic inducer CCN3 (NOV, nephroblastoma overexpressed) is a matricellular protein of the CCN family, which also includes CCN1 (CYR61), CCN2 (CTGF), CCN4 (WISP-1), CCN5 (WISP-2), and CCN6 (WISP-3). CCN3 is broadly expressed in derivatives of all three germ layers during mammalian development, and its deranged expression is associated with vascular injury and a broad range of tumors. We have shown that CCN3 promotes proangiogenic activities in vascular endothelial cells through integrin receptors and induces neovascularization in vivo (Lin, C. G., Leu, S. J., Chen, N., Tebeau, C. M., Lin, S. X., Yeung, C. Y., and Lau, L. F. (2003) J. Biol. Chem. 278, 24200–24208). In this study, we show that CCN3 is highly expressed in granulation tissue of cutaneous wounds 5–7 days after injury and is capable of inducing responses in primary fibroblasts consistent with wound healing. Purified CCN3 supports primary skin fibroblast adhesion through integrins α5β1 and α6β1 and induces fibroblast chemotaxis through integrin αvβ5. We show that CCN3 is a novel ligand of αvβ5 in a solid phase binding assay. Although not mitogenic on its own, CCN3 also enhances basic fibroblast growth factor-induced DNA synthesis. Furthermore, CCN3 up-regulates MMP-1 and PAI-1 expression but interacts with TGF-β1 in an antagonistic or synergistic manner to regulate the expression of specific genes. These findings, together with its angiogenic activity, support a role for CCN3 in cutaneous wound healing in skin fibroblasts and establish its matricellular mode of action through integrin receptors.

• Publication year

  2005

• Venue

  Journal of Biological Chemistry

• Publication date

  2005-03-04

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M404903200PMID 15611078
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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