Use of hypoxia-inducible factor signal transduction pathway to measure O2 levels and modulate growth factor pathways.
Use of hypoxia-inducible factor signal transduction pathway to measure O2 levels and modulate growth factor pathways.
复制标题
使用缺氧诱导因子信号转导途径来测量 O2 水平并调节生长因子途径。
DOI：
10.1046/j.1524-475x.2003.11620.x
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Mustoe,ThomasA
中科院分区：
文献类型：
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作者：
Mogford,JonE;Roy,NakshatraK;Cross,KevinJ;Mustoe,ThomasA
已知组织po2水平可直接调节皮肤组织损伤修复反应的许多过程，包括细胞分化和迁移、细胞外基质合成和成熟，以及内源性和外源性生长因子的有效性。因此，氧气很可能是决定任何组织愈合能力的关键变量。随着组织PO2测量的进步，对皮肤伤口愈合的理解也取得了重大进展，在过去的几十年里，PO2测量从植入式探针发展到现在包括转录因子缺氧诱导因子- 1 （HIF - 1）等分子工具。HIF‐1调节驱动细胞对缺氧适应性反应的基因的表达，并在其启动子序列中具有HIF‐1结合序列，称为缺氧反应元件。分子生物学技术现在允许利用HIF‐1/缺氧反应元件通路来驱动潜在易感异位基因的表达。在这里，我们展示了缺氧反应元件在缺氧驱动的转化生长因子β信号组件Smad3的体外表达和荧光素酶在体内对缺血性缺氧的检测的实用性。Smad3是转化生长因子- β超家族信号转导的积极影响因子。这些方法是亨特及其同事在过去40年里所倡导的最新研究成果。（伤口报告2003；11:49 96 - 503）
Tissue PO2levels are known to directly modulate numerous processes involved in the reparative response to cutaneous tissue injury, including cell differentiation and migration, extracellular matrix synthesis and maturation, and effectiveness of endogenous and exogenous growth factors. Oxygen is therefore likely the critical variable determining the healing capabilities of any tissue. Significant advances in the understanding of cutaneous wound healing progressed with advances in the measurement of tissue PO2, which has advanced over the past several decades from implantable probes to now include molecular tools such as the transcription factor hypoxia inducible factor‐1 (HIF‐1). HIF‐1 modulates the expression of genes that drive the cellular adaptive response to hypoxia and possess the HIF‐1 binding sequence named hypoxia response element within their promoter sequence. Molecular biology techniques are now allowing exploitation of the HIF‐1/hypoxia response element pathway to drive the expression of potential vulnerary ectopic genes. Here we show the utility of the hypoxia response element for hypoxia‐driven expression of the transforming growth factor‐β–signaling component Smad3 in vitro and the in vivo detection of ischemic hypoxia using luciferase. Smad3 is a positive effector of transforming growth factor‐β superfamily signal transduction. Such approaches are the latest evolution of work championed by Hunt and colleagues over the past 4 decades.(WOUND REP REG 2003;11:496–503)