A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy
J. Clin. Invest. Anja Fritsch, et al. 118:1669 doi:10.1172/JCI34292 [
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Figure 7Mitten deformities of the extremities result from excessive contractile fibrosis. (
A) H&E staining showed dermal-epidermal separation (arrows) in the fore paw of an 80-day-old
Col7a1flNeo/flNeo mouse. The cellularity of the dermis was higher than that of
Col7a1WT/WT mice. (
B) van Gieson–elastica staining demonstrated distinct elastic fibers in
Col7a1WT/WT mouse skin, whereas the elastic fibers were strongly reduced in the skin of
Col7a1flNeo/flNeo mice. (
C–
G) Key players of inflammatory/fibrotic processes were assessed by immunofluorescence staining. Nuclei were stained with DAPI (blue). (
C) Positive staining of CD11b, a marker for monocytes, dendritic cells, and macrophages, revealed the presence of inflammatory cells (red) in the
Col7a1flNeo/flNeo dermis. (
D) Expression of active TGF-β1 (red) was enhanced in the dermis of
Col7a1flNeo/flNeo compared with
Col7a1WT/WT mice. (
E) Expression of CTGF (red) increased in both the dermis and the epidermis in
Col7a1flNeo/flNeo mice. (
F) A high number of α-SMA–positive myofibroblasts (red), which are not associated with vessels, were present in the dermis in
Col7a1flNeo/flNeo mice. Green stain denotes α
6 integrin. (
G) Tenascin C (green) was strongly upregulated in the dermis of
Col7a1flNeo/flNeo mice. Scale bars: 100 μm.
