In human wounds, the classical a1 a2 and a3 chains were studied at the mRNA level revealing increased R428 expression in fibroblast-like cells and in endothelial cells of newly formed vessels. Collagen VI gene expression was not detected in smooth muscle cells or in myoepithelial cells of eccrine glands. We could show that in granulation tissue of wounds of wild type mice the classical a1, a2 and a3 chain-containing collagen VI was more strongly expressed than in unwounded skin. The widespread deposition of the protein in dermis indicates that collagen VI is abundantly secreted by fibroblasts. In ICG-001 addition, in wounded skin of wild type mice the a5 chain was up-regulated in the epineurium of newly formed nerves and the a6 chain in the tissue below the wound, but not within the granulation tissue. These results indicate that collagen VI is involved in the wound healing process and that the novel chains could play a more specific role than the broadly expressed classical ones. Up-regulation of collagen VI containing the classical chains was also detected in spontaneously fibrotic skin of tight skin mice and in bleomycin induced lung fibrosis. Indeed, using the bleomycin model of skin fibrosis, we also found up-regulation of the a3 chain in the dermis and of the a5 and a6 chains in blood vessels, indicating that collagen VI is generally up-regulated in fibrotic tissue. Similarly, the a6 chain is expressed at higher levels in fibrotic muscle of Duchenne muscular dystrophy patients. Interestingly, it was recently shown that a proteolytic fragment of collagen VI a1 chain is significantly elevated in the serum of patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis and in a rat model of liver fibrosis. However, in contrast to the hypertrophic scars or keloids occurring in patients with a collagen VI myopathies, we did not observe such disturbed wound healing in the Col6a1 null mice. Most likely this can be explained by the fact that mice have a lesser tendency to overshooting wound healing than humans.