药学学报, 2014, 49(2): 151-157
引用本文:
贾慧珍, KASIM Vivi, 徐志玲, 杨力, 吴寿荣. 低氧应激因子PHD2与血管新生相关疾病[J]. 药学学报, 2014, 49(2): 151-157.
JIA Hui-zhen, KASIM Vivi, XU Zhi-ling, YANG Li, WU Shou-rong. Hypoxia-responsive factor PHD2 and angiogenic diseases[J]. Acta Pharmaceutica Sinica, 2014, 49(2): 151-157.

低氧应激因子PHD2与血管新生相关疾病
贾慧珍1,2, KASIM Vivi1,2, 徐志玲1,2, 杨力1,2, 吴寿荣1,2
1. 重庆大学生物工程学院生物流变科学与技术教育部重点实验室, 重庆 400044;
2. 重庆大学国家"111计划"生物力学与组织修复工程学科创新引智基地, 重庆 400044
摘要:
PHDs家族是低氧应激的重要调控因子,通过调控低氧诱导因子HIFs的稳定性和活性,使细胞和组织适应低氧应激环境。其中,PHD2作为PHDs家族中的重要一员,是低氧诱导因子HIF-1的关键调控因子。近年研究表明,PHD2不仅在缺血性疾病的血管新生中起重要作用,还能通过调控肿瘤生长、转移等相关基因的表达,影响肿瘤微环境下肿瘤的生长及转移。本文就PHD2的分子调控机制及其在生理病理过程中的作用机制进行综述,重点介绍PHD2在血管再生治疗和肿瘤血管新生中的作用,以及目前PHD2作为治疗靶标的开发应用研究。
关键词:    低氧应激      PHD2      血管新生治疗      肿瘤血管新生     
Hypoxia-responsive factor PHD2 and angiogenic diseases
JIA Hui-zhen1,2, KASIM Vivi1,2, XU Zhi-ling1,2, YANG Li1,2, WU Shou-rong1,2
1. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China;
2. "111" Project Laboratory of Biomechanics and Tissue Repair, Chongqing University, Chongqing 400044, China
Abstract:
Prolyl-4-hydroxylase domain (PHDs) family is one of the most important regulatory factors in hypoxic stress. PHD2 plays a critical role in cells and tissues adaptation to the low oxygen environment. Its hydroxylation activity regulates the stability and transcriptional activity of the hypoxia-inducible factor 1 (HIF-1), which is the key factor in response to hypoxic stress. Subsequently, PHD2 acts as an important factor in oxygen homeostasis. Studies have shown that PHD2, through its regulation on HIF-1, plays an important role in the post-ischemic neovascularization. Furthermore, under hypoxic condition, PHD2 also regulates other pathways that positively regulate angiogenesis factors HIF-1 independently. Moreover, recently, several evidences have also shown that PHD2 also affects tumor growth and metastasis in a tumor microenvironment. Based on these facts, PHD2 have been considered as a potential therapeutic target both in treating ischemic diseases and tumors. Here, we review the molecular regulation mechanism of PHD2 and its physiological and pathological functions. We focus on the role of PHD2 in both therapeutic angiogenesis for ischemic disease and tumor angiogenesis, and the current progress in utilizing PHD2 as a therapeutic target.
Key words:    hypoxia    PHD2    angiogenesis therapy    tumor angiogenesis   
收稿日期: 2013-10-08
基金项目: 国家自然科学基金资助项目(81372202,31301119);中央高校基本科研业务费(CQDXWL-2012-118,CQDXWL-2012-116);重庆市基础与前沿研究项目(cstc2013jcyjA10077).
通讯作者: 吴寿荣
Email: shourongwu@hotmail.com
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