HYPOXIA INDUCIBLE FACTOR-1. & DELAYED WOUND HEALING

研究者是加州大学旧金山分校弗朗西斯科的整形外科副教授。他感兴趣的 导致正常和延迟伤口愈合的细胞机制，特别是与糖尿病有关的细胞机制 和转录因子缺氧诱导因子-1（HIF-1）。 他正在用小鼠模型研究糖尿病如何改变小鼠体内葡萄糖、乳酸盐、胰岛素或IGF-1的水平。 创伤并可能损害HIF-1 α蛋白合成，降低HIF-1调节基因（VEGF， HO-1、NOS 2）和延迟愈合。他将（目标1）将HIF-I_蛋白水平、细胞因子活性与HIF-I_蛋白水平、细胞因子活性和细胞因子活性之间的关系联系起来。 转录因子、HIF-1调节蛋白（VEGF、HO-1、NOS 2）的表达和创伤 在瘦素受体缺陷型（db/db）2型糖尿病小鼠及其非糖尿病同窝出生小鼠中的愈合。他 提出a）增加或减少糖尿病患者皮肤成纤维细胞中的HIF-10蛋白水平， 皮肤与HIF-1转录活性和VEGF、HO-1表达的可比变化相关。 B）增加或减少糖尿病和非糖尿病小鼠中的HIF-1 α蛋白 c）增加糖尿病患者中HIF-1 α水平， 伤口加速愈合，而非糖尿病伤口中HIF-I α水平的降低延迟愈合。他还 目的2：研究糖尿病伤口中葡萄糖、乳酸盐、胰岛素或IGF-1水平的改变如何影响伤口愈合 环境影响HIF-1 α和延迟伤口愈合。他提出：a）生理相关水平 葡萄糖、乳酸盐、胰岛素或IGF-1在细胞上模拟伤口环境并改变HIF-I水平， B）操纵葡萄糖、乳酸盐、胰岛素或IGF-1浓度改变伤口的HIF-1 α水平和 c）在糖尿病伤口中发现的葡萄糖、乳酸盐、胰岛素或IGF-1的水平改变 环境抑制HIF-1蛋白翻译（_. 确定糖尿病引起的HIF-1通路的改变，可能会改善这些疾病的治疗。 问题伤口

The investigator is an Associate Professor of Plastic Surgery at UC, San Francisco. He is interested in the cellular mechanisms that lead to normal and delayed wound healing especially as it pertains to diabetes and the transcription factor hypoxia inducible factor-1 (HIF-1). Using a mouse model he is examining how diabetes alters levels of glucose, lactate, insulin, or IGF-1 in the wound and may impair HIF-lo_ protein synthesis, decreased expression of HIF-1 regulated genes (VEGF, HO-1, NOS 2) and delayed healing. He will (Aim 1) correlate the levels of HIF-I_ protein, activity of the transcription factor, expression of several HIF-1 regulated proteins (VEGF, HO-1, NOS 2), and wound healing in leptin receptor-deficient (db/db) Type 2 diabetic mice and their non-diabetic littermates. He proposed that a) Increasing or decreasing HIF-lo_ protein levels in dermal fibroblasts derived from diabetic skin is associated with a comparable change in HIF-1 transcriptional activity, and expression of VEGF, HO- 1 and NOS 2 in culture, b) Increasing or decreasing HIF-I_ protein in the diabetic and non-diabetic mouse wounds results in similar changes of HIF-1 transcriptional activity, c) Increasing HIF-lo_ levels in diabetic wounds accelerate healing and decreasing HIF-I(_ levels in non-diabetic wounds delays healing. He also will (Aim 2) investigate how the altered levels of glucose, lactate, insulin, or IGF-1 in the diabetic wound environment influence HIF-I(_ and delay wound healing. He proposes that a) Physiologically relevant levels of glucose, lactate, insulin, or IGF-1 on cells mimic the wound environment and alter HIF-I_ levels and function, b) Manipulating glucose, lactate, insulin, or IGF-1 concentrations wounds alters HIF-I(_ levels and influences healing, c) Altered levels of glucose, lactate, insulin, or IGF-1 found in the diabetic wound environment inhibit protein translation of HIF-I(_. Identifying alterations in the HIF-1 pathway due to diabetes, may lead to improved therapy for these problem wounds.