CCN2 expression by fibroblasts is not required for cutaneous tissue repair.

The CCN family of matricellular proteins, which includes CCN2 and CCN1, is believed to have a major in vivo role in controlling tissue morphogenesis and repair. In adult skin, the proadhesive matricellular protein connective tissue growth factor (CTGF/CCN2) is specifically up-regulated in fibrosis and wound healing. In mice, CCN2 is required for dermal fibrogenesis, but whether CCN2 is required for cutaneous tissue repair is unknown. To address this question, in this report we subjected adult mice bearing a fibroblast-specific deletion of CCN2 to the dermal punch model of cutaneous tissue repair. Loss of CCN2 did not appreciably affect the kinetics of tissue repair, collagen content, or the number of α-smooth muscle actin-positive cells. CCN1 (cyr61), which has in vitro effect similar to CCN2, is also induced in cutaneous tissue repair. Fibroblast-specific CCN1/CCN2 double knockout mice were also generated; loss of both CCN1 and CCN2 together did not appreciably affect cutaneous tissue repair. However, loss of CCN2 resulted in impaired recruitment of NG2-positive pericyte-like cells to the wound area. Collectively, these results indicate that neither CCN2 nor CCN1 is essential for cutaneous tissue repair; CCN2 appears to be required for recruitment of pericyte-like cells and may represent a specific antifibrotic target.