缺氧诱导因子与肠道辐射损伤的研究进展

杜继聪; 蔡建明

doi:10.11889/j.1000-3436.2018.rrj.36.010101

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缺氧诱导因子与肠道辐射损伤的研究进展

综述 | 更新时间：2021-12-10

- 缺氧诱导因子与肠道辐射损伤的研究进展
- Research progress of hypoxia-inducible factor and radiation-induced intestinal injury
- 辐射研究与辐射工艺学报 2018年36卷第1期
- 作者机构：
  
  1.第二军医大学海军医学系上海 200433
- 作者简介：
  
  [ "杜继聪, 男, 1992年12月生, 2015年6月毕业于第二军医大学, 现为中国人民解放军第二军医大学硕士研究生", "DU Jicong (male) was born in December 1992, and received his bachelor's degree in clinical medicine from Second Military Medical University in 2015. Now he studies in Second Military Medical University as a postgraduate" ]
  蔡建明, 博士, 教授, E-mail:cjm882003@163.comPh.D. CAI Jianming, professor, E-mail: cjm882003@163.com
- 基金信息：
  
  国家自然科学基金重点项目(11635014)
- DOI：10.11889/j.1000-3436.2018.rrj.36.010101
  中图分类号：
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杜继聪, 蔡建明. 缺氧诱导因子与肠道辐射损伤的研究进展[J]. 辐射研究与辐射工艺学报, 2018,36(1):010101-5.

Jicong DU, Jianming CAI. Research progress of hypoxia-inducible factor and radiation-induced intestinal injury[J]. Journal of Radiation Research and Radiation Processing, 2018,36(1):010101-5.
杜继聪, 蔡建明. 缺氧诱导因子与肠道辐射损伤的研究进展[J]. 辐射研究与辐射工艺学报, 2018,36(1):010101-5. DOI： 10.11889/j.1000-3436.2018.rrj.36.010101.

Jicong DU, Jianming CAI. Research progress of hypoxia-inducible factor and radiation-induced intestinal injury[J]. Journal of Radiation Research and Radiation Processing, 2018,36(1):010101-5. DOI： 10.11889/j.1000-3436.2018.rrj.36.010101.

摘要

腹部、盆腔的晚期肿瘤患者在接受肿瘤放射治疗时，射线对肠道正常组织也会造成明显的损伤。研究发现，上调体内缺氧诱导因子（Hypoxia-inducible factor，HIF）水平能起到防护肠道组织辐射损伤的作用。通过脯氨酸羟化酶抑制剂等上调体内HIF水平，减轻肠道上皮细胞、肠道隐窝干细胞损伤程度，维持肠道屏障完整性；上调血管内皮生长因子表达水平，保护肠道微血管内皮；调控NF-kB、炎症因子分泌以及树突状细胞的免疫功能，减缓肠道辐射损伤的炎症反应。本文还对HIF与肿瘤的关系进行了讨论。

Abstract

Patients with abdominal and pelvic tumors may receive radiotherapy which would cause injury to normal intestinal tissue cells. Recent studies demonstrated that increased hypoxia-inducible factor (HIF) can protect the intestinal tissue from radiation-induced damage. Mechanically, increased HIF could reduce the damage of intestinal epithelial cells and intestinal crypt stem cells to maintain the integrity of epithelial barrier, protecting the intestinal microvascular endothelium cells via up-regulating the expression of vascular endothelial growth factor. Moreover, the up-regulated HIF reduced inflammatory response by regulating the nuclear translocation of NF-kB, the secretion of inflammatory cytokines, and the function of dendritic cells. The relationship between HIF and tumor was also discussed.

关键词

缺氧诱导因子肠道辐射损伤肿瘤

Keywords

Hypoxia-inducible factorRadiation-induced intestinal injuryTumor

references

J W Denham , M Hauer-Jensen . Radiation induced bowel injury: a neglected problem . Lancet , 2013 . 382 (9910 ):2046 -2047 . DOI:10.1016/s0140-6736(13)61946-7http://doi.org/10.1016/s0140-6736(13)61946-7 .

H J Andreyev , B E Benton , A Lalji , 等 . Algorithm-based management of patients with gastrointestinal symptoms in patients after pelvic radiation treatment (ORBIT): a randomised controlled trial . Lancet , 2013 . 382 (9910 ):2084 -2092 . DOI:10.1016/s0140-6736(13)61648-7http://doi.org/10.1016/s0140-6736(13)61648-7 .

J Atkinson , A A Kapralov , N Yanamala , 等 . A mitochondria-targeted inhibitor of cytochrome c peroxi-dase mitigates radiation-induced death . Nature Co-mmunications , 2011 . 2 497 DOI:10.1038/ncomms1499http://doi.org/10.1038/ncomms1499 .

L G Burdelya , V I Krivokrysenko , T C Tallant , 等 . An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models . Science , 2008 . 320 (5873 ):226 -230 . DOI:10.1126/science.1154986http://doi.org/10.1126/science.1154986 .

A M Farese , T J MacVittie . Filgrastim for the treatment of hematopoietic acute radiation syndrome . Drugs of Today , 2015 . 51 (9 ):537 -548 . DOI:10.1358/dot.2015.51.9.2386730http://doi.org/10.1358/dot.2015.51.9.2386730 .

M Mangoni , M Sottili , C Gerini , 等 . A PPAR-gamma agonist protects from radiation-induced intestinal toxicity . United European Gastroenterology Journal , 2017 . 5 (2 ):218 -226 . DOI:10.1177/2050640616640443http://doi.org/10.1177/2050640616640443 .

B Keith , R S Johnson , M C Simon . HIF1a and HIF2α: sibling rivalry in hypoxic tumour growth and progression . Nature Reviews Cancer , 2011 . 12 (1 ):9 -22 . DOI:10.1038/nrc3183http://doi.org/10.1038/nrc3183 .

G L Semenza . Hypoxia-inducible factors in physiology and medicine . Cell , 2012 . 148 (3 ):399 -408 . DOI:10.1016/j.cell.2012.01.021http://doi.org/10.1016/j.cell.2012.01.021 .

S K Ramakrishnan , Y M Shah . Role of intestinal HIF-2α in health and disease . Annual Review of Physiology , 2016 . 78 (1 ):301 -325 . DOI:10.1146/annurev-physiol-021115-105202http://doi.org/10.1146/annurev-physiol-021115-105202 .

E B Rankin , A J Giaccia . Hypoxic control of metastasis . Science , 2016 . 352 (6282 ):175 -180 . DOI:10.1126/science.aaf4405http://doi.org/10.1126/science.aaf4405 .

V H Haase . HIF-prolyl hydroxylases as therapeutic targets in erythropoiesis and iron metabolism . Hemodialysis international. International Symposium on Home Hemodialysis , 2017 . 21 (Suppl S1 ):S110 -S124 . DOI:10.1111/hdi.12567http://doi.org/10.1111/hdi.12567 .

M C Manresa , C T Taylor . Hypoxia inducible factor (HIF) hydroxylases as regulators of intestinal epithelial barrier function . Cellular and Molecular Gastroenterology and Hepatology , 2017 . 3 (3 ):303 -315 . DOI:10.1016/j.jcmgh.2017.02.004http://doi.org/10.1016/j.jcmgh.2017.02.004 .

H K Eltzschig , D L Bratton , S P Colgan . Targeting hypoxia signaling for the treatment of ischaemic and inflammatory diseases . Nature Reviews Drug Dis-covery , 2014 . 13 (11 ):852 -869 . DOI:10.1038/nrd4422http://doi.org/10.1038/nrd4422 .

E Marks , B J Goggins , J Cardona , 等 . Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis . Inflammatory Bowel Diseases , 2015 . 21 (2 ):267 -275 . DOI:10.1097/mib.0000000000000277http://doi.org/10.1097/mib.0000000000000277 .

G Hoppe , S Yoon , B Gopalan , 等 . Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity . Proceedings of the National Academy of Sciences of the United States of America , 2016 . 113 (18 ):E2516 -2525 . DOI:10.1073/pnas.1523005113http://doi.org/10.1073/pnas.1523005113 .

C M Taniguchi , Y R Miao , A N Diep , 等 . PHD inhibition mitigates and protects against radiation-induced gastro-intestinal toxicity via HIF2 . Science Translational Medicine , 2014 . 6 (236 ):236ra264 DOI:10.1126/scitranslmed.3008523http://doi.org/10.1126/scitranslmed.3008523 .

J Karhausen , G T Furuta , J E Tomaszewski , 等 . Epithelial hypoxia-inducible factor-1 is protective in murine experi-mental colitis . The Journal of Clinical Investigation , 2004 . 114 (8 ):1098 -1106 . DOI:10.1172/jci21086http://doi.org/10.1172/jci21086 .

E P Cummins , F Seeballuck , S J Keely , 等 . The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis . Gastroenterology , 2008 . 134 (1 ):156 -165 . DOI:10.1053/j.gastro.2007.10.012http://doi.org/10.1053/j.gastro.2007.10.012 .

J Rotolo , B Stancevic , J Zhang , 等 . Anti-ceramide antibody prevents the radiation gastrointestinal syndrome in mice . The Journal of Clinical Investigation , 2012 . 122 (5 ):1786 -1790 . DOI:10.1172/jci59920http://doi.org/10.1172/jci59920 .

M K Ayrapetov , C Xu , Y Sun , 等 . Activation of Hif1α by the prolylhydroxylase inhibitor dimethyoxalyglycine decreases radiosensitivity . PLoS one , 2011 . 6 (10 ):e26064 DOI:10.1371/journal.pone.0026064http://doi.org/10.1371/journal.pone.0026064 .

S Han , W Xu , Z Wang , 等 . Crosstalk between the HIF-1 and toll-like receptor/nuclear factor-kappaB pathways in the oral squamous cell carcinoma microenvironment . Oncotarget , 2016 . 7 (25 ):37773 -37789 . DOI:10.18632/oncotarget.9329http://doi.org/10.18632/oncotarget.9329 .

X Zhang , S Li , M Li , 等 . Hypoxia-inducible factor-1alpha mediates the toll-like receptor 4 signaling pathway leading to anti-tumor effects in human hepatocellular carcinoma cells under hypoxic conditions . Oncology Letters , 2016 . 12 (2 ):1034 -1040 . DOI:10.3892/ol.2016.4705http://doi.org/10.3892/ol.2016.4705 .

D Bandarra , J Biddlestone , S Mudie , 等 . HIF-1alpha restricts NF-kappaB-dependent gene expression to control innate immunity signals . Disease Models & Mechanisms , 2015 . 8 (2 ):169 -181 . DOI:10.1242/dmm.017285http://doi.org/10.1242/dmm.017285 .

N Lin , M C Simon . Hypoxia-inducible factors: key regulators of myeloid cells during inflammation . The Journal of Clinical Investigation , 2016 . 126 (10 ):3661 -3671 . DOI:10.1172/jci84426http://doi.org/10.1172/jci84426 .

S A Hirota , K Fines , J Ng , 等 . Hypoxia-inducible factor signaling provides protection in Clostridium difficile-induced intestinal injury . Gastroenterology , 2010 . 139 (1 ):259 -269 . DOI:10.1053/j.gastro.2010.03.045http://doi.org/10.1053/j.gastro.2010.03.045 .

E P Cummins , E Berra , K M Comerford , 等 . Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity . Proceedings of the National Academy of Sciences of the United States of America , 2006 . 103 (48 ):18154 -18159 . DOI:10.1073/pnas.0602235103http://doi.org/10.1073/pnas.0602235103 .

F R Greten , L Eckmann , T F Greten , 等 . IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer . Cell , 2004 . 118 (3 ):285 -296 . DOI:10.1016/j.cell.2004.07.013http://doi.org/10.1016/j.cell.2004.07.013 .

E T Clambey , E N McNamee , J A Westrich , 等 . Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa . Proceedings of the National Academy of Sciences of the United States of America , 2012 . 109 (41 ):E2784 -2793 . DOI:10.1073/pnas.1202366109http://doi.org/10.1073/pnas.1202366109 .

M Higashiyama , R Hokari , H Hozumi , 等 . HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis . Journal of Leukocyte Biology , 2012 . 91 (6 ):901 -909 . DOI:10.1189/jlb.1011518http://doi.org/10.1189/jlb.1011518 .

E V Dang , J Barbi , H Y Yang , 等 . Control of TH17/Treg balance by hypoxia-inducible factor 1 . Cell , 2011 . 146 (5 ):772 -784 . DOI:10.1016/j.cell.2011.07.033http://doi.org/10.1016/j.cell.2011.07.033 .

W Wan , K Peng , M Li , 等 . Histone demethylase JMJD1A promotes urinary bladder cancer progression by enhancing glycolysis through coactivation of hypoxia inducible factor 1alpha . Oncogene , 2017 . 36 (27 ):3868 -3877 . DOI:10.1038/onc.2017.13http://doi.org/10.1038/onc.2017.13 .

F Zhou , J Du , J Wang . Albendazole inhibits HIF-1alpha-dependent glycolysis and VEGF expression in non-small cell lung cancer cells . Molecular and Cellular Biochemistry , 2017 . 428 (1-2 ):171 -178 . DOI:10.1007/s11010-016-2927-3http://doi.org/10.1007/s11010-016-2927-3 .

G L Semenza . Hypoxia-inducible factors: coupling glucose metabolism and redox regulation with induction of the breast cancer stem cell phenotype . The EMBO Journal , 2017 . 36 (3 ):252 -259 . DOI:10.15252/embj.201695204http://doi.org/10.15252/embj.201695204 .

W Tang , K Dong , K Li , 等 . MEG3, HCN3 and linc01105 influence the proliferation and apoptosis of neuroblastoma cells via the HIF-1alpha and p53 pathways . Scientific Reports , 2016 . 6 36268 DOI:10.1038/srep36268http://doi.org/10.1038/srep36268 .

J Yin , B Ni , W G Liao , 等 . Hypoxia-induced apoptosis of mouse spermatocytes is mediated by HIF-1alpha through a death receptor pathway and a mitochondrial pathway . Journal of Cellular Physiology , 2017 . DOI:10.1002/jcp.25974http://doi.org/10.1002/jcp.25974 .

E Sasabe , Y Tatemoto , D Li , 等 . Mechanism of HIF-1alpha-dependent suppression of hypoxia-induced apoptosis in squamous cell carcinoma cells . Cancer Science , 2005 . 96 (7 ):394 -402 . DOI:10.1111/j.1349-7006.2005.00065.xhttp://doi.org/10.1111/j.1349-7006.2005.00065.x .

J D Gordan , J A Bertout , C J Hu , 等 . HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity . Cancer Cell , 2007 . 11 (4 ):335 -347 . DOI:10.1016/j.ccr.2007.02.006http://doi.org/10.1016/j.ccr.2007.02.006 .

J D Gordan , C B Thompson , M C Simon . HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation . Cancer Cell , 2007 . 12 (2 ):108 -113 . DOI:10.1016/j.ccr.2007.07.006http://doi.org/10.1016/j.ccr.2007.07.006 .

H Harada . Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radioresistance . Journal of Radiation Research , 2016 . 57 (Suppl 1 ):i99 -i105 . DOI:10.1093/jrr/rrw01http://doi.org/10.1093/jrr/rrw01 .

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