이전|다음

식이 메티오닌 보충이 방사선 조사 후 쥐의 조혈을 촉진한다

  • role： Contribute equally, First author同等贡献者, 第一作者
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Wei-Wei Zhang12,  
  • role： Contribute equally同等贡献者
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Yang Xiang12,  
  • role： Contribute equally同等贡献者
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Li Chen12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

    Department of Nutrition, The Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

Shao-Ting Liu123,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Chuan-Chuan Lin12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Jiu-Xuan Li12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Li-Xin Xiang12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Nan-Xi Chen12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Dong-Ling Shi12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Yang-Yang Zhang12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Xue-Ying Wang12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Lan-Yue Hu12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Sai Chen12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Ya Luo12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Cheng-Ning Tan12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Pei-Pei Xue12,  
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

Yang-Zhou Jiang12,  
  • Affiliation：

    Neuro-Oncology and Stem Cell Research Laboratory, CHOC Children’s Research Institute, Children’s Hospital of Orange County (CHOC), Orange, CA 92868-3874, USA

    Department of Neurology, University of California - Irvine School of Medicine, Orange, CA 92868, USA

Sheng-Wen Calvin Li45,  
  • role： Corresponding author通信作者
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

  • Email：yangzx88@tmmu.edu.cn
  • Introduction：* Zhen-Xing Yang yangzx88@tmmu.edu.cn
Zhen-Xing Yang12*,  
  • role： Corresponding author通信作者
  • Affiliation：

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

    Department of Thoracic Surgery, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

  • Email：daijigang@tmmu.edu.cn
  • Introduction：Ji-Gang Dai daijigang@tmmu.edu.cn
Ji-Gang Dai26*,  
  • role： Corresponding author通信作者
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

  • Email：zhongjunli@tmmu.edu.cn
  • Introduction：Zhong-Jun Li zhongjunli@tmmu.edu.cn
Zhong-Jun Li12*,  
  • role： Corresponding author通信作者
  • Affiliation：

    Department of Blood Transfusion, Laboratory Medicine Center, the Second Affiliated Hospital, Army Medical University, Chongqing 400037, China

    Hematopoietic Acute Radiation Syndrome Medical and Pharmaceuti-cal Basic Research Innovation Center, Ministry of Education of the People’s Republic of China, Chongqing 400037, China

  • Email：louise-r-q@163.com
  • Introduction：Qian Ran louise-r-q@163.com
Qian Ran12*

추상적인

BackgroundWith the increasing risk of nuclear exposure, more attention has been paid to the prevention and treat-ment of acute radiation syndrome (ARS). Although amino acids are key nutrients involved in hematopoietic regula-tion, the impacts of amino acids on bone marrow hematopoiesis following irradiation and the associated mecha-nisms have not been fully elucidated. Hence, it is of paramount importance to study the changes in amino acid metabolism after irradiation and their effects on hematopoiesis as well as the related mechanisms.MethodsThe content of serum amino acids was analyzed using metabolomic sequencing. The survival rate and body weight of the irradiated mice were detected after altering the methionine content in the diet. Extracel-lular matrix (ECM) protein analysis was performed via proteomics analysis. Inflammatory factors were examined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry, Western blotting, and immunofluorescence were employed to determine the mechanism by which S100 calcium-binding protein A4 (S100A4) regulates macrophage polarization.ResultsThe survival time of irradiated mice was significantly associated with alterations in multiple amino acids, particularly methionine. A high methionine diet promoted irradiation tolerance, especially in the recovery of bone marrow hematopoiesis, yet with dose limitations. Folate metabolism could partially alleviate the dose bottleneck by reducing the accumulation of homocysteine. Mechanistically, high methionine levels maintained the abundance of ECM components, including collagens and glycoproteins, in the bone marrow post-irradiation, among which the level of S100A4 was significantly changed. S100A4 regulated macrophage polarization via the STAT3 pathway, inhibited bone marrow inflammation and facilitated the proliferation and differentiation of hematopoietic stem/pro-genitor cells.ConclusionsWe have demonstrated that an appropriate elevation in dietary methionine enhances irradia-tion tolerance in mice and explains the mechanism by which methionine regulates bone marrow hematopoiesis after irradiation.

키워드

Irradiation;Methionine;macrophage;S100A4;Bone marrow hematopoiesis

References

  1. 1..
    Waselenko JK, Macvittie TJ, Blakely WF, Pesik N, Wiley AL, Dickerson WE, et al. Medical management of the acute radiation syndrome: recommen-dations of the strategic national stockpile radiation working group. Ann Intern Med. 2004;140(12):1037-51.
  2. 2..
    Weiss W. Radiological protection issues arising during and after the fukushima nuclear reactor accident-memorandum of TG84 of ICRP. Radiat Prot Dosimetry. 2016;171(1):20-2.
  3. 3..
    JrEaton EB, Varney TR. Mesenchymal stem cell therapy for acute radiation syndrome: innovative medical approaches in military medicine. Mil Med Res. 2015;2:2.
  4. 4..
    Kiang JG, Olabisi AO. Radiation: a poly-traumatic hit leading to multi-organ injury. Cell Biosci. 2019;9:25.
  5. 5..
    Mendelson A, Frenette PS. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat Med. 2014;20(8):833-46.
  6. 6..
    Lee-Thedieck C, Schertl P, Klein G. The extracellular matrix of hematopoi-etic stem cell niches. Adv Drug Deliv Rev. 2022;181:114069.
  7. 7..
    Lapidot T, Dar A, Kollet O. How do stem cells find their way home? Blood.2005;106(6):1901-10.
  8. 8..
    Mitchell CA, Verovskaya EV, Calero-Nieto FJ, Olson OC, Swann JW, Wang X, et al. Stromal niche inflammation mediated by IL-1 signalling is a targeta-ble driver of haematopoietic ageing. Nat Cell Biol. 2023;25(1):30-41.
  9. 9..
    Girotra M, Monnard C, Konz T, Sizzano F, Goulet L, Godin JP, et al. Mineral and amino acid profiling of different hematopoietic populations from the mouse bone marrow. Int J Mol Sci. 2020;21(17):6444.
  10. 10..
    Richter FC, Obba S, Simon AK. Local exchange of metabolites shapes immunity. Immunology. 2018;155(3):309-19.
  11. 11..
    Simsek T, Kocabas F, Zheng J, Deberardinis RJ, Mahmoud AI, Olson EN, et al. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell. 2010;7(3):380-90.
  12. 12..
    Maynard RS, Hellmich C, Bowles KM, Rushworth SA. Acute myeloid leu-kaemia drives metabolic changes in the bone marrow niche. Front Oncol.2022;12:924567.
  13. 13..
    Taya Y, Ota Y, Wilkinson AC, Kanazawa A, Watarai H, Kasai M, et al. Deplet-ing dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation. Science. 2016;354(6316):1152-5.
  14. 14..
    Du C, Liu C, Yu K, Zhang S, Fu Z, Chen X, et al. Mitochondrial serine catabolism safeguards maintenance of the hematopoietic stem cell pool in homeostasis and injury. Cell Stem Cell. 2024;31(10):1484-500.e9.
  15. 15..
    Li C, Wu B, Li Y, Chen J, Ye Z, Tian X, et al. Amino acid catabolism regulates hematopoietic stem cell proteostasis via a GCN2-eIF2α axis. Cell Stem Cell. 2022;29(7):1119-34.e7.
  16. 16..
    Sommerkamp P, Altamura S, Renders S, Narr A, Ladel L, Zeisberger P, et al. Differential alternative polyadenylation landscapes mediate hematopoi-etic stem cell activation and regulate glutamine metabolism. Cell Stem Cell. 2020;26(5):722-38.e7.
  17. 17..
    Shukla J, Chatterjee S, Thakur VS, Premachandran S, Checker R, Poduval TB. L-arginine reverses radiation-induced immune dysfunction: the need for optimum treatment window. Radiat Res. 2009;171(2):180-7.
  18. 18..
    Duffy PH, Lewis SM, Mayhugh MA, Mccracken A, Thorn BT, Reeves PG, et al. Effect of the AIN-93M purified diet and dietary restriction on survival in Sprague-Dawley rats: implications for chronic studies. J Nutr.2002;132(1):101-7.
  19. 19..
    Aissa AF, Amaral CLD, Venancio VP, Machado CDS, Hernandes LC, Santos P, et al. Methionine-supplemented diet affects the expression of cardiovas-cular disease-related genes and increases inflammatory cytokines in mice heart and liver. J Toxicol Environ Health A. 2017;80(19-21):1116-28.
  20. 20..
    Li JT, Yang H, Lei MZ, Zhu WP, Su Y, Li KY, et al. Dietary folate drives methio-nine metabolism to promote cancer development by stabilizing MAT IIA. Signal Transduct Target Ther. 2022;7(1):192.
  21. 21..
    Guo H, Chou WC, Lai YJ, Liang KX, Tam JW, Brickey WJ, et al. Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites. Science. 2020;370(6516):eaay9097.
  22. 22..
    Bergiers I, Andrews T, Vargel Bolukbasi O, Buness A, Janosz E, Lopez-Anguita N, et al. Single-cell transcriptomics reveals a new dynamical function of transcription factors during embryonic hematopoiesis. Elife.2018;7:e29312.
  23. 23..
    Feng W, Jasin M. BRCA2 suppresses replication stress-induced mitotic and G1 abnormalities through homologous recombination. Nat Commun.2017;8(1):525.
  24. 24..
    Zhang XM, Hou LJ, Li FJ, Zhang WW, Wu C, Xiang LX, et al. Piezo1-mediated mechanosensation in bone marrow macrophages promotes vascular niche regeneration after irradiation injury. Theranostics.2022;12(4):1621-38.
  25. 25..
    Nagarajan A, Lasher AT, Morrow CD, Sun LY. Long term methionine restriction: Influence on gut microbiome and metabolic characteristics. Aging Cell. 2024;23(3):e14051.
  26. 26..
    Gao X, Sanderson SM, Dai Z, Reid MA, Cooper DE, Lu M, et al. Dietary methionine influences therapy in mouse cancer models and alters human metabolism. Nature. 2019;572(7769):397-401.
  27. 27..
    Hasan T, Arora R, Bansal AK, Bhattacharya R, Sharma GS, Singh LR. Disturbed homocysteine metabolism is associated with cancer. Exp Mol Med. 2019;51(2):1-13.
  28. 28..
    Miousse IR, Tobacyk J, Melnyk S, James SJ, Cheema AK, Boerma M, et al. One-carbon metabolism and ionizing radiation: a multifaceted interac-tion. Biomol Concepts. 2017;8(2):83-92.
  29. 29..
    Zhang DQ, Fang P, Jiang XH, Nelson J, Moore JK, Kruger WD, et al. Severe hyperhomocysteinemia promotes bone marrow-derived and resident inflammatory monocyte differentiation and atherosclerosis in LDLr/CBS-deficient mice. Circ Res. 2012;111(1):37-49.
  30. 30..
    Klamer S, Voermans C. The role of novel and known extracellular matrix and adhesion molecules in the homeostatic and regenerative bone mar-row microenvironment. Cell Adh Migr. 2014;8(6):563-77.
  31. 31..
    Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK. Extracellular matrix structure. Adv Drug Deliv Rev. 2016;97:4-27.
  32. 32..
    Xiong JL, Yan LL, Zou C, Wang K, Chen MJ, Xu B, et al. Integrins regulate stemness in solid tumor: an emerging therapeutic target. J Hematol Oncol. 2021;14(1):177.
  33. 33..
    Jiang YF, Zhang HY, Wang J, Liu YL, Luo T, Hua H. Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy. J Hematol Oncol. 2022;15(1):34.
  34. 34..
    Sutherland TE, Dyer DP, Allen JE. The extracellular matrix and the immune system: a mutually dependent relationship. Science.2023;379(6633):eabp8964.
  35. 35..
    Hou S, Jiao Y, Yuan Q, Zhai J, Tian T, Sun K, et al. S100A4 protects mice from high-fat diet-induced obesity and inflammation. Lab Invest.2018;98(8):1025-38.
  36. 36..
    Ampomah PB, Cai B, Sukka SR, Gerlach BD, JrYurdagul A, Wang X, et al. Macrophages use apoptotic cell-derived methionine and DNMT3A during efferocytosis to promote tissue resolution. Nat Metab.2022;4(4):444-57.
  37. 37..
    Petit V, Parcelier A, Mathe C, Barroca V, Torres C, Lewandowski D, et al. TRIM33 deficiency in monocytes and macrophages impairs resolution of colonic inflammation. EBioMedicine. 2019;44:60-70.
  38. 38..
    Chiu M, Taurino G, Bianchi MG, Bussolati O. The role of amino acids in the crosstalk between mesenchymal stromal cells and neoplastic cells in the hematopoietic niche. Front Cell Dev Biol. 2021;9:714755.
  39. 39..
    Huang D, Chen C, Xie L, Yu Z, Zheng J. Hematopoietic stem cell metabo-lism and stemness. Blood Sci. 2019;1(1):12-8.
  40. 40..
    Korimerla N, Wahl DR. Interactions between radiation and one-carbon metabolism. Int J Mol Sci. 2022;23(3):1919.
  41. 41..
    Batra V, Sridhar S, Devasagayam TP. Enhanced one-carbon flux towards DNA methylation: effect of dietary methyl supplements against gamma-radiation-induced epigenetic modifications. Chem Biol Interact.2010;183(3):425-33.
  42. 42..
    JrBeard RS, Reynolds JJ, Bearden SE. Hyperhomocysteinemia increases permeability of the blood-brain barrier by NMDA receptor-dependent regulation of adherens and tight junctions. Blood. 2011;118(7):2007-14.
  43. 43..
    Tripathi M, Singh BK, Zhou J, Tikno K, Widjaja A, Sandireddy R, et al. Vita-min B12 and folate decrease inflammation and fibrosis in NASH by pre-venting syntaxin 17 homocysteinylation. J Hepatol. 2022;77(5):1246-55.
  44. 44..
    Wilkinson AC, Morita M, Nakauchi H, Yamazaki S. Branched-chain amino acid depletion conditions bone marrow for hematopoietic stem cell transplantation avoiding amino acid imbalance-associated toxicity. Exp Hematol. 2018;63:12-6.e1.
  45. 45..
    Fang ZJ, Li YB, Wang JW, Wang XR, Huang LR, Sun LJ, et al. Alleviative effect of threonine on cadmium-induced liver injury in mice. Biol Trace Elem Res. 2023;201(9):4437-46.
  46. 46..
    Cunningham A, Erdem A, Alshamleh I, Geugien M, Pruis M, Pereira-Martins DA, et al. Dietary methionine starvation impairs acute myeloid leukemia progression. Blood. 2022;140(19):2037-52.
  47. 47..
    Liu SQ, Zhang HL, Li YA, Zhang YN, Bian YY, Zeng YQ, et al. S100A4 enhances protumor macrophage polarization by control of PPAR-γ-dependent induction of fatty acid oxidation. J Immunother Cancer.2021;9(6):e002548.
  48. 48..
    Aissa AF, Tryndyak V, De Conti A, Melnyk S, Gomes TD, Bianchi ML, et al. Effect of methionine-deficient and methionine-supplemented diets on the hepatic one-carbon and lipid metabolism in mice. Mol Nutr Food Res. 2014;58(7):1502-12.
  49. 49..
    Yan J, Horng T. Lipid metabolism in regulation of macrophage functions. Trends Cell Biol. 2020;30(12):979-89.
  50. 50..
    Xia T, Zhang M, Lei W, Yang R, Fu S, Fan Z, et al. Advances in the role of STAT3 in macrophage polarization. Front Immunol. 2023;14:1160719.
  51. 51..
    Li S, Yao JC, Oetjen KA, Krambs JR, Xia J, Zhang J, et al. IL-1β expression in bone marrow dendritic cells is induced by TLR2 agonists and regulates HSC function. Blood. 2022;140(14):1607-20.
  52. 52..
    Singh VK, Romaine PLP, Newman VL. Biologics as countermeasures for acute radiation syndrome: where are we now? Expert Opin Biol Ther.2015;15(4):465-71.
  53. 53..
    Stenke L, Hedman C, Lindberg ML, Lindberg K, Valentin J. The acute radia-tion syndrome need for updated medical guidelines. J Radiol Prot. 2022. .

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