PMC

Relative quantification of (A) TGF-β and (B) SMAD3 expression in irradiated and non-irradiated murine skin samples, quantified by RT-PCR.

Histological analysis of control and fibronectin-treated radiated wounds. (A) H&E. (B) Sirius red reveals increased fascicular and horizontal collagen deposition in fibronectin-treated wounds. (C) Anti-MPO IHC shows fewer neutrophils in fibronectin-treated wounds. (D) Anti-F4/80 IHC demonstrates fewer macrophages in fibronectin-treated wounds. (E) Anti-CD31 IHC demonstrates increased endothelial cell presences in fibronectin-treated wounds. Scale bars represent 50 µm.

(A) Heat map of reverse phase protein array of paired irradiated and non-irradiated human skin samples. Samples are listed by date collected and labeled NML (normal) or XRT (radiated). Green corresponds to higher and red to lower relative expression. (B) Cropped Western blot of fibronectin expression in four pairs of human skin samples. (C) Relative quantification of fibronectin gene expression in paired human skin samples by qRT-PCR.

(A) Photo of a patient with a non-healing lower extremity wound. Note the skin discoloration associated with radiation injury. (B) Representative example of H&E (left) and Sirius red (right) staining of paired normal (top) and irradiated (bottom) human skin samples, demonstrating abnormally thick stratum corneum (a), thin epidermis (b), disordered collagen (c), and chronic inflammatory cells (d) characteristic of radiation-induced skin damage. Scale bars represent 100 µm.

(A) Flow diagram for experimental methodology. (B) qRT-PCR demonstrating that fibronectin expression is significantly downregulated after radiation of mouse skin 4–6 weeks after exposure. (C) Irradiated skin heals significantly slower than normal skin at all time points (p < 0.05). (D) Representative normal (top) and irradiated (bottom) wounds at days 0, 12, and 24 post-wounding. (E) Topical application of fibronectin at the time of wounding is associated with significantly accelerated wound healing at all time points (p < 0.05). (F) Representative radiated wounds with vehicle control (top) and fibronectin treatment (bottom) at days 0, 14, and 21.