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低氧诱导因子-1的病理生理及相关药物研究进展

冯世杰 马秀娟 宗英 毛煜 张晓冬 弓雪莲 张晓芳 陆国才

冯世杰, 马秀娟, 宗英, 毛煜, 张晓冬, 弓雪莲, 张晓芳, 陆国才. 低氧诱导因子-1的病理生理及相关药物研究进展[J]. 药学实践与服务, 2014, 32(3): 161-166. doi: 10.3969/j.issn.1006-0111.2014.03.001
引用本文: 冯世杰, 马秀娟, 宗英, 毛煜, 张晓冬, 弓雪莲, 张晓芳, 陆国才. 低氧诱导因子-1的病理生理及相关药物研究进展[J]. 药学实践与服务, 2014, 32(3): 161-166. doi: 10.3969/j.issn.1006-0111.2014.03.001
FENG Shijie, MA Xiujuan, ZONG Ying, MAO Yu, ZHANG Xiaodong, GONG Xuelian, ZHANG Xiaofang, LU Guocai. Progress in pathophysiology and related drug development of hypoxia-inducible factor-1[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(3): 161-166. doi: 10.3969/j.issn.1006-0111.2014.03.001
Citation: FENG Shijie, MA Xiujuan, ZONG Ying, MAO Yu, ZHANG Xiaodong, GONG Xuelian, ZHANG Xiaofang, LU Guocai. Progress in pathophysiology and related drug development of hypoxia-inducible factor-1[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(3): 161-166. doi: 10.3969/j.issn.1006-0111.2014.03.001

低氧诱导因子-1的病理生理及相关药物研究进展

doi: 10.3969/j.issn.1006-0111.2014.03.001
基金项目: 科技部重大专项"重大新药创制"(2010ZXG0900X-005),上海市公共卫生重点实验室建设计划(12GWZX0501).

Progress in pathophysiology and related drug development of hypoxia-inducible factor-1

  • 摘要: 低氧诱导因子-1(hypoxia-inducible factors, HIF-1)是介导哺乳动物和人体细胞低氧适应性反应的主要核转录因子,是专一调节氧稳态的关键物质。HIF-1对胚胎的正常发育,软骨及骨的形成等多种生理过程起保护及促进作用,也与肿瘤、糖尿病及其并发症等多种缺血低氧性疾病密切相关。HIF-1在这些疾病中的分子机制已成为目前的研究热点,笔者就HIF-1的结构特征、调控机制、生物学效用及在药物研发等方面进行综述。
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    [2] Duval E, Ieclercq S, Elissalde JM, et al. Hypoxia-inducible factor 1alpha inhibits the fibroblast like rmrkers typeⅠand type Ⅲ collagen during hypoxia-induced chondrocyte redifferentiation:hypoxia not only induces type collagen and aggrecan,but it a1so inhibits typeⅠand type Ⅲ collagen in the hypoxia-indudble factor 1alpha-dependent redifferentiation of chondrocytes[J]. Arthr Rheum, 2009, 60(10): 3038-3048.
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    [17] Wang Y, Liu Y, Malek SN, et al. Targeting HIF-1α eliminates cancer stem cells in hematological malignancies[J].Cell Stem Cell, 2011, 8(4): 399-411.
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    [19] Luo W, Hu H, Chang R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1[J].Cell, 2011, 145(5): 732-744.
    [20] Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics[J].Oncogene, 2010, 29(5): 625-634.
    [21] Rey S, Semenza GL. Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodeling[J].Cardiovase Res, 2010, 86(2): 236-242.
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    [27] Takiyama Y, Harumi T, Watanable J, et al. Tubular injury in a rat model of type 2 diabetes is prevented by metformin: a possible role of HIF-lα expression and oxygen metabolism[J].Diabetes, 2011, 60(3): 981-992.
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    [29] Zhang H, Qian DZ, Tan YS, et al. Digoxin and other cardiac glycosides inhibit HIF-l alpha synthesis and block tumor growth[J].Proc Natl Acad Sci USA, 2008, 105(50): 19579-19586.
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  • 收稿日期:  2013-03-19
  • 修回日期:  2013-10-18

低氧诱导因子-1的病理生理及相关药物研究进展

doi: 10.3969/j.issn.1006-0111.2014.03.001
    基金项目:  科技部重大专项"重大新药创制"(2010ZXG0900X-005),上海市公共卫生重点实验室建设计划(12GWZX0501).

摘要: 低氧诱导因子-1(hypoxia-inducible factors, HIF-1)是介导哺乳动物和人体细胞低氧适应性反应的主要核转录因子,是专一调节氧稳态的关键物质。HIF-1对胚胎的正常发育,软骨及骨的形成等多种生理过程起保护及促进作用,也与肿瘤、糖尿病及其并发症等多种缺血低氧性疾病密切相关。HIF-1在这些疾病中的分子机制已成为目前的研究热点,笔者就HIF-1的结构特征、调控机制、生物学效用及在药物研发等方面进行综述。

English Abstract

冯世杰, 马秀娟, 宗英, 毛煜, 张晓冬, 弓雪莲, 张晓芳, 陆国才. 低氧诱导因子-1的病理生理及相关药物研究进展[J]. 药学实践与服务, 2014, 32(3): 161-166. doi: 10.3969/j.issn.1006-0111.2014.03.001
引用本文: 冯世杰, 马秀娟, 宗英, 毛煜, 张晓冬, 弓雪莲, 张晓芳, 陆国才. 低氧诱导因子-1的病理生理及相关药物研究进展[J]. 药学实践与服务, 2014, 32(3): 161-166. doi: 10.3969/j.issn.1006-0111.2014.03.001
FENG Shijie, MA Xiujuan, ZONG Ying, MAO Yu, ZHANG Xiaodong, GONG Xuelian, ZHANG Xiaofang, LU Guocai. Progress in pathophysiology and related drug development of hypoxia-inducible factor-1[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(3): 161-166. doi: 10.3969/j.issn.1006-0111.2014.03.001
Citation: FENG Shijie, MA Xiujuan, ZONG Ying, MAO Yu, ZHANG Xiaodong, GONG Xuelian, ZHANG Xiaofang, LU Guocai. Progress in pathophysiology and related drug development of hypoxia-inducible factor-1[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(3): 161-166. doi: 10.3969/j.issn.1006-0111.2014.03.001
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