EGFR Enhances Early Healing After Cutaneous Incisional Wounding

Abstract

The epidermal growth factor receptor (EGFR) has been implicated in the regulation of wound healing. In order to directly evaluate the role of endogenous EGFR in cutaneous incisional wound healing, we examined EGFR null- and wild-type skin after injury. By 5 d after wounding, re-epithelialization was complete in all EGFR wild-type wounds, but in only 40% of EGFR null wounds. Delayed wound closure in EGFR null skin was accompanied by an increase in edema, longer lasting and more prominent eschar, and increased distance between apposing wound edges. EGFR altered neutrophil and mast cell infiltration, and enhanced angiogenesis. EGFR enhanced epithelial proliferation during the first 3 d following injury, although proliferation was greater in EGFR null wounds at 5 d. Although migration was decreased in EGFR null keratinocytes cultured with standard medium or in medium supplemented with transforming growth factor-alpha when compared with controls, the addition of the wound-associated motogen keratinocyte growth factor eliminated the differences between genotypes. Epithelial migration into the wound was decreased in EGFR null skin, suggesting that both EGFR-dependent and -independent mechanisms regulate migration during wound healing. These data demonstrate that EGFR regulates multiple facets of cutaneous wound healing, including inflammation, wound contraction, proliferation, migration, and angiogenesis.

Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats

“…Galiano et al 30 demonstrated that pharmacological VEGF therapy in diabetics enhances neovascularization with a clinically significant effect. The mechanism for this effect is through a stimulation of local angiogenesis, enhanced expression of growth factors including PDGF and FGF-2, and a systemic mobilization of bone marrow-derived stem cells.…”

The Roles of Growth Factors in Keratinocyte Migration

“…Although other HER receptors participate in signaling, EGFR is the dominant EGF-family receptor in KCs, as evidenced by the severe impairment of wound reepithelialization observed in EGFR knockout mice. 26 EGFR is expressed throughout the epidermis, with its most prominent expression in the basal layer. 27 EGFR is activated in an autocrine manner by ligands synthesized by KCs, activated in a paracrine manner by ligands synthesized by platelets, lymphocytes, macrophages, or FBs, or transactivated by angiotensin II-or antimicrobial peptide hCAP18/LL-37-induced HB-EGF autocrine signaling.…”

Current role of antibody therapy in patients with metastatic colorectal cancer

“…EGFR therapy in conjunction with surgery must be considered very carefully as it is demonstrated that EGFR regulates multiple facets of wound healing, including inflammation, wound contraction, proliferation, migration and angiogenesis (Repertinger et al, 2004). In head and neck cancer, a small study with eight patients (Harari et al, 2003) receiving elective neck dissection after curative intended radiotherapy in combination with Cx, the length of hospital stay was not prolonged and no postoperative complications was found.…”