缺氧诱导因子-1α在缺血性脑卒中模型中介导神经干-祖细胞作用机制的研究进展

doi:10.3969/j.issn.1006-9771.2017.03.015

摘要/Abstract

摘要： 缺氧诱导因子-1α (HIF-1α)是一种缺氧应答因子。脑缺血缺氧时,HIF-1α表达上调,调控下游基因表达,对脑缺血后能量代谢障碍的改善以及微循环的建立具有重要意义。神经干-祖细胞的再生能促进脑梗死的功能恢复。HIF-1α可能通过Notch通路、Wnt/β-catenin通路等机制,介导神经干-祖细胞增殖、分化。

关键词: 缺血性脑卒中, 缺氧诱导因子-1α, 神经干-祖细胞, 综述

Abstract: Hypoxia inducible factor-1α is a kind of hypoxia response factor. Acute cerebral ischemia and anoxia can induce up-regulation of hypoxia inducible factor-1α, and the downstream genes, which plays a role in both the energy metabolism and collateral circulation after cerebral ischemia. Neural stem and progenitor cells regeneration also benefit the functional outcome after ischemic stroke. Hypoxia inducible factor-1α may induce proliferation and differentiation of neural stem and progenitor cells through Notch, Wnt/β-catenin pathways, etc., in the ischemic stroke model.

Key words: ischemic stroke, hypoxia inducible factor-1α, neural stem and progenitor cells, review

中图分类号:

R743.3

张东圆, 李明, 王正则, 张文冉, 许晓丹, 张丽莹, 田沈. 缺氧诱导因子-1α在缺血性脑卒中模型中介导神经干-祖细胞作用机制的研究进展[J]. 《中国康复理论与实践》, 2017, 23(3): 319-322.

ZHANG Dong-yuan, LI Ming, WANG Zheng-ze, ZHANG Wen-ran, XU Xiao-dan, ZHANG Li- ying, TIAN Shen. Mechanism of Neural Stem and Progenitor Cells Mediated by Hypoxia Inducible Factor-1α in Ischemic Stroke Model (review)[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2017, 23(3): 319-322.

参考文献

[1] Lindvall O, Kokaia Z. Stem cells in human neurodegenerative disorders-time for clinical translation? [J]. J Clin Invest, 2010, 120(1): 29-40.
[2] Semenza GL, Wing GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation [J]. Mol Cell Biol, 1992, 12(12): 5447-5454.
[3] Loboda A, Jozkowicz A, Dulak J. HIF-l and HIF-2 transcription factors–similar but not identical [J]. Mol Cells, 2010, 29(5): 435-442.
[4] Adams JM, Difazio LT, Rolandelli RH, et al. HIF-1: a key mediator in hypoxia [J]. Acta Physiol Hung, 2009, 96(1): 19-28.
[5] Vadlapatla RK, Vadlapudi AD, Mitra AK. Hypoxia-Inducible Factor-1 (HIF-1): A potential target for intervention in ocular neovascular diseases [J]. Curr Drug Targets, 2013, 14(8): 919-935.
[6] Duan C. Hypoxia-inducible factor 3 biology: complexities and emerging themes [J]. Am J Physiol Cell Physiol, 2016, 310(4): 260-269.
[7] 朱婷娜,徐恩. 缺氧诱导因子1α在脑缺血中的作用及其机制[J]. 国际脑血管病杂志, 2012, 20(4): 310-314.
[8] Liu YV, Baek JH, Zhang H, et al. RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha [J]. Mol Cell, 2007, 25(26): 207-217.
[9] Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress [J]. Mol Cell, 2010, 40(2): 294-309.
[10] Cunningham LA, Candelario K. Roles for HIF-1α in neural stem cell function and the regenerative response to stroke [J]. Behav Brain Res, 2012, 227(2): 410-417.
[11] Aimone JB, Li Y, Lee SW, et al. Regulation and function of adult neurogenesis: from genes to cognition [J]. Physiol Rev, 2014, 94(4): 991-1026.
[12] De La Rosa-Prieto C, De Moya-Pinilla M, Saiz-Sanchez D, et al. Olfactory and cortical projections to bulbar and hippocampal adult-born neurons [J]. Front Neuroanat, 2015, 9: 4.
[13] Luskin MB. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain sub-ventricular zone [J]. Neuron, 2003, 11(1): 173-189.
[14] Gage FH. Mammalian neural stem cells [J]. Science, 2000, 287(5457): 1433-1438.
[15] Xu C, Loh HH, Law PY. Effects of addictive drugs on adult neural stem/progenitor cells [J]. Cell Mol Life Sci, 2016, 73(2): 327-348.
[16] Kondo T, Raff M. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells [J]. Science, 2000, 289(5485): 1754-1757.
[17] Ohab JJ, Fleming S, Blesch A, et al. A neurovascular niche for neuro-genesis after stroke [J]. J Neurosci, 2006, 26(50): 13007-13016.
[18] Roitbak T, Li L, Cunningham LA. Neural stem/progenitor cells promote endothelial cell morphogenesis and protect endothelial cells against ischemia via HIF-1alpha-regulated VEGF signaling [J]. J Cereb Blood Flow Metab, 2008, 28(9): 1530-1542.
[19] Xiong Y, Mahmood A, Chopp M. Angiogenesis, neurogenesis and brain recovery of function following injury [J]. Curr Opin Investig Drugs, 2010, 11(3): 298-308.
[20] Pasantes-Morales H, Ramos-Mandujano G, Hernández-Benítez R. Taurine enhances proliferation and promotes neuronal specification of murine and human neural stem/progenitor cells [J]. Adv Exp Med Biol, 2015, 803: 457-472.
[21] Thored P, Wood J, Arvidsson A, et al. Long-term neuroblast migration along blood vessels in an area with transient angiogenesis and increased vascularization after stroke [J]. Stroke, 2007, 38(11): 3032-3039.
[22] Marti-Fabregas J, Romaguera-Ros M, Gomez-Pinedo U, et al. Proliferation in the human ipsilateral sub-ventricular zone after ischemic stroke [J]. Ann Neurosci, 2010, 7(3): 134-135.
[23] Nakayama D, Matsuyama T, Ishibashi-Ueda H, et al. Injury-induced neural stem/progenitor cells in post-stroke human cerebral cortex [J]. Eur J Neurosci, 2010, 31(1): 90-98.
[24] Dooley D, Vidal P, Hendrix S. Immunopharmacological intervention for successful neural stem cell therapy: new perspectives in CNS neurogenesis and repair [J]. Pharmacol Ther, 2014, 41(1): 21-31.
[25] Breunig JJ, Silbereis J, Vaccarino FM, et al. Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus [J]. Proc Natl Acad Sci U S A, 2007, 104(51): 20558-20563.
[26] Cheng YL, Park JS, Manzanero S, et al. Evidence that collaboration between HIF-1α and Notch-1 promotes neuronal cell death in ischemic stroke [J]. Neurobiol Dis, 2014, 62: 286-295.
[27] Kriska J, Honsa P, Dzamba D, et al. Manipulating Wnt signaling at different subcellular levels affects the fate of neonatal neural stem/progenitor cells [J]. Brain Res, 2016, 1651: 73-87.
[28] Inestrosa NC, Varela-Nallar L. Wnt signalling in neuronal differentiation and development [J]. Cell Tissue Res, 2015, 359(1): 215-223.
[29] Morris DC, Zhang ZG, Wang Y, et al. Wnt expression in the adult rat subventricular zone after stroke [J]. Neurosci Lett, 2007, 418(2): 170-174.
[30] Gao Z, Ure K, Ables JL, et al. Neurod1 is essential for the survival and maturation of adult-born neurons [J]. Nat Neurosci, 2009, 12(9): 1090-1092.
[31] Kuwabara T, Hsieh J, Muotri A, et al. Wnt-mediated activation of Neuro D1 and retro-elements during adult neurogenesis [J]. Nat Neurosci, 2009, 12(9): 1097-1105.
[32] Mazumdar J, O'Brien WT, Johnson RS, et al. O 2 regulates stem cells through Wnt/beta-catenin signalling [J]. Nat Cell Biol, 2010, 12(10): 1007-1013.
[33] Li L, Candelario KM, Thomas K, et al. Hypoxia inducible factor-1α (HIF-1α) is required for neural stem cell maintenance and vascular stability in the adult mouse SVZ [J]. J Neurosci, 2014, 34(50): 16713-16719.
[34] Roitbak T, Surviladze Z, Cunningham LA. Continuous expression of HIF-1alpha in neural stem/progenitor cells [J]. Cell Mol Neurobiol, 2011, 31(1): 119-133.
[35] Fagerlund M, Pérez Estrada C, Jaff N, et al. Neural stem/progenitor cells transplanted to the hypoglossal nucleus integrates with the host CNS in adult rats and promotes motor neuron survival [J]. Cell Transplant, 2012, 21(4): 739-747.
[36] Harms KM, Li L, Cunningham LA. Murine neural stem/progenitor cells protect neurons against ischemia by HIF-1alpha-regulated VEGF signaling [J]. PLoS One, 2010, 5(3): e9767.
[37] Sugai K, Fukuzawa R, Shofuda T, et al. Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases [J]. Mol Brain, 2016, 9(1): 85.
[38] Duncan K, Gonzales-Portillo GS, Acosta SA, et al. Stem cell-paved biobridges facilitate stem transplant and host brain cell interactions for stroke therapy [J]. Brain Res, 2015, 1623: 160-165.
[39] 陈太邦,赵建华. 内源性NSPCs与脊髓损伤治疗的研究进展[J]. 创伤外科杂志, 2012, 14(4): 373-376.
[40] Chapman KZ, Ge R, Monni E. Inflammation without neuronal death triggers striatal neurogenesis comparable to stroke [J]. Neurobiol Dis, 2015, 83: 1-15.