J Vet Sci.  2006 Jun;7(2):105-109. 10.4142/jvs.2006.7.2.105.

Topical application of epidermal growth factor accelerates wound healing by myofibroblast proliferation and collagen synthesis in rat

• Kwon YB
• Kim HW
• Roh DH
• Yoon SY
• Baek RM
• Kim JY
• Kweon HY
• Lee KG
• Park YH
• Lee JH

• KMID: 1059193
• DOI: http://doi.org/10.4142/jvs.2006.7.2.105

Abstract

Recombinant human epidermal growth factor (rhEGF) stimulates the proliferation and migration of epithelial cells in human cell culture systems and animal models of partial-thickness skin wounds. This study investigated the effect of a topical rhEGF ointment on the rate of wound healing and skin re-epithelialization in a rat full thickness wound model, and verified whether or not the rhEGF treatment affected both myofibroblast proliferation and collagen synthesis in the dermis. When rhEGF (10 microgram/g ointment) was applied topically twice a day for 14 days, there was significantly enhanced wound closure from the 5th to the 12th day compared with the control (ointment base treatment) group. A histological examination at the postoperative 7th day revealed that the rhEGF treatment increased the number of proliferating nuclear antigen immunoreactive cells in the epidermis layer. In addition, the immunoreactive area of alpha-smooth muscle actin and the expression of prolyl 4-hydroxylase were significantly higher than those of the control group. Overall, a topical treatment of rhEGF ointment promotes wound healing by increasing the rate of epidermal proliferation and accelerating the level of wound contraction related to myofibroblast proliferation and collagen deposition.

Keyword

alpha-smooth muscle actin; proliferating cell nuclear antigen; prolyl 4-hydroxylase; recombinant human epidermal growth factor; wound healing

MeSH Terms

Actins/genetics/metabolism
Administration, Topical
Animals
Cell Proliferation/drug effects
Collagen/*biosynthesis
Epidermal Growth Factor/*administration&dosage/*pharmacology
Gene Expression Regulation
Male
Myoblasts, Skeletal/*drug effects
Proliferating Cell Nuclear Antigen/genetics/metabolism
Rats
Rats, Sprague-Dawley
Wound Healing/*drug effects

Figure

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  Fig. 1 The degree of wound healing in the rhEGF (10 µg/g) treatment group and control (ointment base) group. Residual Wound Area (%) = [R(2~12)/R(1)]×100, where R(1) and R(2~12) represent the area remaining at postoperative days 1 and day 2~12, respectively. The wound-healing curve was fitted using the Boltzman equation and the half heal time (HT50). Each bar represents the mean ± SE. *p < 0.01 compared with the control (ointment base) group.

• 

  Fig. 2 The effect of rhEGF (10 µg/g) on the proliferating cell nuclear antigen (PCNA) and alpha-smooth muscle actin (α-SMA) immunoreactivity in a full-thickness excision wound 7 days after the wound. (A): PCNA immunoreactivity of the control group, (B): PCNA immunoreactivity of the rhEGF treated group, (C): α-SMA immunoreactivity of the control group, (D): α-SMA immunoreactivity of the rhEGF treated group. The control group was treated with the ointment base. The arrow indicates PCNA (A and B) or α-SMA (C and D) immunoreactivity. Scale bar = 200 µm.

• 

  Fig. 3 Image analysis data of proliferating cell nuclear antigen (PCNA) (A) and alpha-smooth muscle actin (α-SMA) immunoreactivity (B) in a full-thickness excision wound at 7 days. The number of PCNA immunoreactive neuron and the area of α-SMA expression were significantly increased in the rhEGF treated group compared with the control (ointment base treatment) group. *p < 0.01 compared with the control group.

• 

  Fig. 4 The effect of the rhEGF (10 µg/g) treatment on the expression of prolyl 4-hydroxylase (P4H) in a full-thickness excision wound at 7 days. (A) The expression pattern of P4H, (B) Density analysis data. The P4H expression level was markedly increased in the rhEGF treated group compared with the control (ointment base treatment) group. *p < 0.01 compared with the control group.

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