Antimycotic Ciclopirox Olamine in the Diabetic Environment Promotes Angiogenesis and Enhances Wound Healing

被引:25
|
作者
Ko, Sae Hee [1 ,2 ]
Nauta, Allison [1 ,3 ]
Morrison, Shane D. [1 ]
Zhou, Hongyan [4 ]
Zimmermann, Andrew [1 ]
Gurtner, Geoffrey C. [1 ,5 ]
Ding, Sheng
Longaker, Michael T. [1 ,5 ]
机构
[1] Stanford Univ, Sch Med, Dept Surg, Hagey Lab Regenerat Med,Div Plast & Reconstruct S, Stanford, CA 94305 USA
[2] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA
[3] Georgetown Univ, Sch Med, Dept Surg, Washington, DC USA
[4] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA
[5] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA
来源
PLOS ONE | 2011年 / 6卷 / 11期
基金
美国国家卫生研究院;
关键词
VEGF EXPRESSION; HYPOXIA; HIF-1-ALPHA; ULCERS; OXYGEN; FOOT; ONYCHOMYCOSIS; IMPAIRMENTS; INDUCTION; TISSUE;
D O I
10.1371/journal.pone.0027844
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Diabetic wounds remain a major medical challenge with often disappointing outcomes despite the best available care. An impaired response to tissue hypoxia and insufficient angiogenesis are major factors responsible for poor healing in diabetic wounds. Here we show that the antimycotic drug ciclopirox olamine (CPX) can induce therapeutic angiogenesis in diabetic wounds. Treatment with CPX in vitro led to upregulation of multiple angiogenic genes and increased availability of HIF-1 alpha. Using an excisional wound splinting model in diabetic mice, we showed that serial topical treatment with CPX enhanced wound healing compared to vehicle control treatment, with significantly accelerated wound closure, increased angiogenesis, and increased dermal cellularity. These findings offer a promising new topical pharmacologic therapy for the treatment of diabetic wounds.
引用
收藏
页数:9
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