The FACIT collagen XII decorates large collagen fibrils within stiff connective tissues. While its mutation or loss causes disorders of connective tissues in humans, its overabundance was described in fibrotic lesions of scleroderma patients and in corneal scarring, indicating a vital role of collagen XII in ECM development and homeostasis. We postulate that collagen XII has the potential to influence tissue properties by linking scaffolding molecules, transmitting signals to cells or by modulating availability of growth factors. We aim to study the roles of dermal collagen XII during reconstitution of the skin following excisional wounding in wild type mice and in mice with fibroblast-specific overexpression of collagen XII. In wild type, collagen XII was strongly deposited into early granulation tissue after injury and persisted at high levels throughout the healing process. The overexpressing mice showed delayed wound healing with enlarged, more cell dense granulation tissue. The number of macrophages was significantly increased. Characterization of macrophage subpopulations revealed that in the collagen XII overexpressing situation, the macrophages maintained an early wound healing (M1-like) phenotype, indicating that overall wound healing was delayed. In vitro interaction studies between macrophages and collagen XII showed that only M1 polarized macrophages were able to adhere to collagen XII, but not unstimulated or M2 polarized macrophages. These findings led to the hypothesis that overproduction of collagen XII favors selective adhesion of M1 polarized pro-inflammatory macrophages causing a delay in wound healing and possibly more severe scarring. In the future, we will characterize the late stages of wound healing and investigate the receptor reservoir that mediates the selective adhesion of M1 polarized macrophages to collagen XII.

Fibroblast-specific overexpression of collagen XII leads to a delay in skin repair