期刊
ACS CHEMICAL BIOLOGY
卷 17, 期 6, 页码 1357-1363出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.2c00382
关键词
-
资金
- Department of Defense Therapeutic Development Award [W81XWH-19-1-0493]
Pressure ulcers (PUs) are chronic wounds that are difficult to heal. The role of matrix metalloproteinases (MMPs) in wound healing and the presence of specific MMPs in PUs were investigated. Higher concentrations of MMP-8, MMP-9, and MMP-14 were found in human PUs compared to healthy tissue. In a mouse model, a selective inhibitor for MMP-9 and MMP-14 accelerated wound closure and improved ulcer stage, suggesting its potential as a treatment for PUs.
Pressure ulcers (PUs) are chronic wounds that lead to amputations and death. Little is known about why PUs are recalcitrant to healing. Wound healing is mediated by matrix metalloproteinases (MMPs). The 24 MMPs in humans each exist in three forms, of which only one is catalytically competent. We analyzed human PU samples using an affinity resin that exclusively binds to the catalytically competent MMPs. We identified by mass spectrometry the active forms of MMP-1, MMP-8, MMP-9, and MMP-14. Concentrations of MMP-8, MMP-9, and MMP-14 were higher in human PUs compared to the healthy tissue, whereas those for MMP-1 did not change. Decreasing levels of active MMP-9 as the PU improved argued for a detrimental role for this enzyme. In a mouse model of PUs, a highly selective inhibitor for MMP-9 and MMP-14, (R)-ND-336, accelerated wound closure in parallel with significant amelioration of ulcer stage. (R)-ND-336 holds promise as a first-in-class treatment for PUs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据