This may allow an increased diffusion into neighbouring tissues, thereby promoting TGF-b signaling. Although collagen VI, predominantly in its classical form, is strongly expressed in wounds, the consequences of its absence are not overt. Immunofluorescence staining for wound healing markers such as a-smooth muscle actin, desmin, the F4/80 epitope or CD31 and for several extracellular matrix proteins and collagen VI binding partners did not show marked differences between wild type and Col6a1 null mice. Only when collagen fibrils at day 7 of wound healing were stained with picrosirus red and visualized by polarization microscopy, a clear difference between wild type and Col6a1 null mice was seen. The Dabrafenib reason for this difference became obvious when the collagen I fibrils in day 7 wounds were visualized in greater detail by electron microscopy. A larger proportion of the fibrils were closely spaced in the Col6a1 null mice than in wild type mice, indicating that collagen VI deficiency alters matrix architecture and possibly biomechanical properties. Similar ultrastructural alterations were also seen in tendons of mice deficient for either collagen VI a1 or a3 chains. In Col6a1 null tendons the diameter distribution of collagen I fibrils was significantly shifted towards thinner fibrils. An SB431542 analysis of fibril density demonstrated a,2.5 fold increase in the Col6a1 null versus wild type tendons and Col6a1 null tendons displayed reduced biomechanical strength and stiffness, which corresponds to the reduced ultimate load and stress of Col6a1 null skin in stretching experiments shown here. Interestingly, ultrastructurally abnormal collagen I fibrils were observed in tendon, but not in cornea, of Col6a1 null mice, indicating a tissue-specific action of collagen VI on collagen I fibrillogenesis. Possibly the role of collagen VI is more pronounced in tissues which are exposed to mechanical stress. Nevertheless, a recent ultrastructural analysis of the skin of a patient with BM carrying a mutation in the collagen VI a2 chain revealed variations in size of collagen I fibrils, flower-like cross sections of collagen I fibrils, as well as thickening and duplication of vascular and nerve basement membranes in the skin strikingly similar to the changes that we detected in Col6a1 null mice.