归巢(生物学)
祖细胞
高氧
伤口愈合
血管生成
医学
内皮祖细胞
伊诺斯
间质细胞
动员
基质细胞衍生因子1
干细胞
内科学
内分泌学
免疫学
趋化因子
CXCR4型
炎症
细胞生物学
一氧化氮
生物
一氧化氮合酶
肺
考古
生态学
历史
作者
Katherine A. Gallagher,Zhao Jun Liu,Min Xiao,Haiying Chen,Lee J. Goldstein,Donald G. Buerk,April E. Nedeau,Stephen R. Thom,Omaida C. Velázquez
摘要
Endothelial progenitor cells (EPCs) are essential in vasculogenesis and wound healing, but their circulating and wound level numbers are decreased in diabetes. This study aimed to determine mechanisms responsible for the diabetic defect in circulating and wound EPCs. Since mobilization of BM EPCs occurs via eNOS activation, we hypothesized that eNOS activation is impaired in diabetes, which results in reduced EPC mobilization. Since hyperoxia activates NOS in other tissues, we investigated whether hyperoxia restores EPC mobilization in diabetic mice through BM NOS activation. Additionally, we studied the hypothesis that impaired EPC homing in diabetes is due to decreased wound level stromal cell-derived factor-1alpha (SDF-1alpha), a chemokine that mediates EPC recruitment in ischemia. Diabetic mice showed impaired phosphorylation of BM eNOS, decreased circulating EPCs, and diminished SDF-1alpha expression in cutaneous wounds. Hyperoxia increased BM NO and circulating EPCs, effects inhibited by the NOS inhibitor N-nitro-L-arginine-methyl ester. Administration of SDF-1alpha into wounds reversed the EPC homing impairment and, with hyperoxia, synergistically enhanced EPC mobilization, homing, and wound healing. Thus, hyperoxia reversed the diabetic defect in EPC mobilization, and SDF-1alpha reversed the diabetic defect in EPC homing. The targets identified, which we believe to be novel, can significantly advance the field of diabetic wound healing.
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