Figure 8. Human RDEB and other chronic wounds display similar molecular alterations.

Wound biopsies were obtained from fresh wounds 3 days after primary excision (Acute wound), from the wound margins of nonhealing chronic venous ulcers, and from wounds of RDEB patients. (A) Wounds were stained for laminin-332 (red) and integrin α6 (green) or for COL7A1 (red). Yellow arrowheads denote the end of the epithelial front in the acute wound. For chronic and RDEB wounds, the epithelial front in the wound margin is shown. Acute wounds showed linear deposition of laminin-332 and regular, primarily basal, expression of integrin α6, whereas in chronic and RDEB wounds, laminin-332 deposition was irregular and integrin α6 expression suprabasal (white arrows). Importantly, in acute wounds, COL7A1 was distinctly present under the healing epidermis, whereas it was irregular and drastically reduced in chronic wounds. Nuclei were visualized with DAPI (blue). Scale bar: 50 μm. (B) Epidermal tongues in wound margins stained for phospho-JNK (green) or phospho-STAT3 (green). Nuclei were counterstained with DAPI (blue). Red lines denote the epidermal-dermal interface. In acute wounds, phospho-JNK and phospho-STAT3 staining was weak and mainly seen in basal keratinocytes, whereas both chronic and RDEB wounds showed strong phospho-JNK and phospho-STAT3 staining in suprabasal keratinocytes. Scale bar: 50 μm.