The Role of Hypoxia-Inducible Factor in Wound Healing
The Role of Hypoxia-Inducible Factor in Wound Healing
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DOI：
10.1089/wound.2013.0520
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发表时间：
2014-05-01
影响因子：
4.9
通讯作者：
Longaker, Michael T.
中科院分区：
文献类型：
--
作者：
Hong, Wan Xing;Hu, Michael S.;Longaker, Michael T.
重要性：伤口愈合不良仍然是美国大量患者的重要健康问题。对局部伤口缺氧的生理反应在确定正常愈合过程的成功中起关键作用。缺氧诱导因子-1（HIF-1）作为氧稳态的主要调节因子，是愈合结果的重要决定因素。HIF-1通过其在整个愈合过程中的细胞迁移、缺氧条件下的细胞存活、细胞分裂、生长因子释放和基质合成中的作用而有助于伤口愈合的所有阶段。HIF-1的正调节剂，如脯氨酰-4-羟化酶抑制剂，已经显示出在促进糖尿病缺血性伤口闭合方面是有益的，并且目前正在进行临床试验，用于治疗几种人类-关键问题：HIF-1缺乏和随后对缺氧刺激的反应失败导致慢性缺氧，这已被证明有助于形成不愈合的溃疡。相比之下，HIF-1的过表达通过其增加肌成纤维细胞分化的作用导致过度的基质产生和沉积而与纤维化疾病有关。因此，HIF-1的正调节因子和负调节因子都提供了重要的治疗靶点，可用于操纵HIF-1的表达，其中已知HIF-1的过量或不足与pathogenicity.Future Directions相关：在伤口愈合过程中靶向HIF-1对组织修复具有许多重要的临床意义。通过调节HIF-1表达来抵消HIF-1信号传导过度或不足的有害影响可能会改善未来对愈合不良伤口的管理。
Significance: Poor wound healing remains a significant health issue for a large number of patients in the United States. The physiologic response to local wound hypoxia plays a critical role in determining the success of the normal healing process. Hypoxia-inducible factor-1 (HIF-1), as the master regulator of oxygen homeostasis, is an important determinant of healing outcomes. HIF-1 contributes to all stages of wound healing through its role in cell migration, cell survival under hypoxic conditions, cell division, growth factor release, and matrix synthesis throughout the healing process.Recent Advances: Positive regulators of HIF-1, such as prolyl-4-hydroxylase inhibitors, have been shown to be beneficial in enhancing diabetic ischemic wound closure and are currently undergoing clinical trials for treatment of several human-ischemia-based conditions.Critical Issues: HIF-1 deficiency and subsequent failure to respond to hypoxic stimuli leads to chronic hypoxia, which has been shown to contribute to the formation of nonhealing ulcers. In contrast, overexpression of HIF-1 has been implicated in fibrotic disease through its role in increasing myofibroblast differentiation leading to excessive matrix production and deposition. Both positive and negative regulators of HIF-1 therefore provide important therapeutic targets that can be used to manipulate HIF-1 expression where an excess or deficiency in HIF-1 is known to correlate with pathogenesis.Future Directions: Targeting HIF-1 during wound healing has many important clinical implications for tissue repair. Counteracting the detrimental effects of excessive or deficient HIF-1 signaling by modulating HIF-1 expression may improve future management of poorly healing wounds.