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Updated: Aug 18, 2026
Murine Model of Wound Healing
Published on: May 28, 2013
Angiogenesis inhibitor TNP-470 inhibits murine cutaneous wound healing
S A Klein1, S J Bond, S C Gupta
1Department of Physiology and Biophysics, Division of Pediatric Surgery, Louisville, Kentucky, 40292, USA.
Background:
TNP-470 (AGM-1470) is a potent inhibitor of angiogenesis with potential therapeutic applications in neoplastic and angio-proliferative diseases. This study evaluated its effect on cutaneous wound healing in a murine dorsal excisional wound model.
Materials And Methods:
Full-thickness wounds (1.60 cm2) were created on the dorsum of homozygous/hairless mice (7 to 9 weeks). Wound areas were measured on alternate days for 16 days. Experimental groups consisted of (1) TNP-470 administered in doses of 0.05, 0.5, and 5.0 mg/kg on Days 0, 2, and 4 or Days 0 through 6; (2) TNP-470 (5.0 mg/kg) coadministered with minocycline (4.0 and 10 mg/kg) on Days 0, 2, and 4; and (3) TNP-470 (5.0 mg/kg on Days 0, 2, and 4) coadministered with topical basic fibroblast growth factor (bFGF) 1. 0 microg/wound on Days 0, 1, and 2. Hematoxylin and eosin staining was used to compare experimental and control wounds.
Results:
TNP-470 administration significantly decreased wound healing in a dose-dependent manner versus controls (P <.05). The 5.0 mg/kg concentration yielded the greatest effect by maintaining an average wound area 20.4% greater than controls and a marked delay in wound healing on H&E staining. Alternate-day dosing was as effective as consecutive day administration. Minocycline did not augment the wound healing inhibition of TNP-470. Coadministration of TNP-470 and bFGF eliminated any rate-altering effect of TNP-470 upon wound healing and resulted in wound areas similar to controls.
Conclusion:
Therapy with TNP-470 induces a significant delay in murine cutaneous wound healing. This effect may be exploited for use in situations where wound healing is excessive and debilitating. Topical application of bFGF can overcome TNP-470-induced wound healing inhibition.
Insights
TNP-470 significantly delays wound healing in mice, with higher doses causing a greater effect. Basic fibroblast growth factor (bFGF) can reverse this inhibition, suggesting therapeutic potential for excessive wound healing.
Area of Science:
- Wound healing research
- Angiogenesis inhibition
- Dermatology
Background:
- TNP-470 (AGM-1470) is a potent angiogenesis inhibitor with therapeutic potential for neoplastic and angio-proliferative diseases.
- This study investigates the impact of TNP-470 on cutaneous wound healing in a murine model.
Purpose of the Study:
- To evaluate the effect of TNP-470 on cutaneous wound healing in mice.
- To determine the dose-dependent effects of TNP-470 on wound closure.
- To assess the potential of minocycline and bFGF to modulate TNP-470's effect on wound healing.
Main Methods:
- Full-thickness excisional wounds were created in hairless mice.
- TNP-470 was administered at various doses and schedules.
- Wound areas were measured, and histological analysis (H&E staining) was performed.
- Combinations with minocycline and topical bFGF were evaluated.
Main Results:
- TNP-470 significantly delayed wound healing in a dose-dependent manner.
- The highest dose (5.0 mg/kg) showed the most pronounced inhibition, with a 20.4% larger wound area compared to controls.
- Minocycline did not enhance TNP-470's inhibitory effect.
- Coadministration with bFGF completely reversed the wound healing inhibition caused by TNP-470.
Conclusions:
- TNP-470 therapy significantly delays murine cutaneous wound healing.
- This inhibitory effect could be beneficial in conditions with excessive wound healing.
- Topical bFGF effectively counteracts TNP-470-induced wound healing delay.
