Accelerated wound healing in mice with a disruption of the thrombospondin 2 gene

Mice that lack the extracellular matrix protein thrombospondin 2 have, amon g several abnormalities, an increase in vascular density, abnormal collagen fibrils, and dermal fibroblasts that are defective in adhesion. These find ings suggested that responses involving these processes, such as wound heal ing, might be altered, To investigate the healing process, excisional wound s were made with the aid of a biopsy punch. Such wounds, observed over a 14 d period, appeared to heal at an accelerated rate and with less scarring i n thrombospondin 2-null mice. Histologic analysis of thrombospondin 2-null wound sites revealed the presence of an irregularly organized and highly va scularized granulation tissue. In addition, thrombospondin 2-null wounds re tained a higher total cellular content, than control wounds. No differences in wound re-epithelization rates were observed, but thrombospondin 2-null epithelia formed rete pegs and were thicker than control epithelia. By immu nohistochemistry, we detected elevated levels and an irregular deposition p attern for fibronectin in thrombospondin 2-null wounds, observations that c orrelated with the abnormal collagen organization in the granulation tissue . Immunostaining for thrombospondin 2 in control wounds showed that the pro tein is present in both early and late wounds, in a scattered cell-associat ed pattern or widely distributed cell- and matrix-associated pattern, respe ctively. Our results suggest that thrombospondin 2 plays a crucial part in the organization and vascularization of the granulation tissue during heali ng, possibly by modulating fibroblast-matrix interactions in early wounds a nd regulating the extent of angiogenesis in late wounds.