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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Systemic Lupus Erythematosus | Review

Megakaryocytic dysfunction in immune thrombocytopenia is linked to autophagy

Authors: Rui-jie Sun, Ning-ning Shan

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Immune thrombocytopenic purpura (ITP) is a multifactorial autoimmune disease characterized by both increased platelet destruction and/or reduced platelet production. Even though they are detected in ≤ 50% of ITP patients, auto-antibodies play a pivotal role in the pathogenesis of ITP. Recent experimental and clinical observations have revealed abnormal autophagy in ITP patients. Autophagy is a catabolic process responsible for the elimination and recycling of cytoplasmic constituents, such as organelles and macromolecules, in eukaryotic cells. Additionally, it triggers cell death or promotes cell survival following various forms of stress, and maintains the microenvironment and stemness of haematopoietic stem cells. The role of autophagy in megakaryopoiesis, thrombopoiesis, and platelet function is slowly being uncovered. The abnormal autophagy in ITP patients may be caused by deletion of autophagy-related genes such as ATG7 and abnormal signalling due to overexpression of mTOR. These changes are thought to affect markers of haematopoietic stem cells, such as CD41 and CD61, and differentiation of megakaryocytes, ultimately decreasing the function and quantity of platelets and leading to the onset of ITP. This review highlights recent evidence on the essential role played by autophagy in megakaryopoiesis, megakaryocyte differentiation, thrombopoiesis, and platelet production. It also discusses the potential of targeting the autophagy pathway as a novel therapeutic approach against ITP.
Literature
1.
2.
Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M, Green-Thompson ZW, et al. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev. 2010;90(4):1383–435.PubMedCrossRef
3.
Gianchecchi E, Delfino DV, Fierabracci A. Recent insights on the putative role of autophagy in autoimmune diseases. Autoimmun Rev. 2014;13(3):231–41.PubMedCrossRef
4.
5.
Li-Harms X, Milasta S, Lynch J, Wright C, Joshi A, Iyengar R, et al. Mito-protective autophagy is impaired in erythroid cells of aged mtDNA-mutator mice. Blood. 2015;125(1):162–74.PubMedPubMedCentralCrossRef
6.
Colosetti P, Puissant A, Robert G, Luciano F, Jacquel A, Gounon P, et al. Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line. Autophagy. 2009;5(8):1092–8.PubMedCrossRef
7.
Pan Q, Gao C, Chen Y, Feng Y, Liu WJ, Liu HF. Update on the role of autophagy in systemic lupus erythematosus: a novel therapeutic target. Biomed Pharmacother. 2015;71:190–3.PubMedCrossRef
8.
Ireland JM, Unanue ER. Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells. J Exp Med. 2011;208(13):2625–32.PubMedPubMedCentralCrossRef
9.
Alirezaei M, Fox HS, Flynn CT, Moore CS, Hebb AL, Frausto RF, et al. Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis. Autophagy. 2009;5(2):152–8.PubMedCrossRef
10.
Huang J, Ge M, Lu S, Shi J, Yu W, Li X, et al. Impaired autophagy in adult bone marrow CD34+ cells of patients with aplastic anemia: possible pathogenic significance. PLoS ONE. 2016;11(3):e0149586.PubMedPubMedCentralCrossRef
11.
Matsuura A, Tsukada M, Wada Y, Ohsumi Y. Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene. 1997;192(2):245–50.PubMedCrossRef
12.
Wang Q, You T, Fan H, Wang Y, Chu T, Poncz M, et al. Rapamycin and bafilomycin A1 alter autophagy and megakaryopoiesis. Platelets. 2017;28(1):82–9.PubMedCrossRef
13.
Raslova H, Baccini V, Loussaief L, Comba B, Larghero J, Debili N, et al. Mammalian target of rapamycin (mTOR) regulates both proliferation of megakaryocyte progenitors and late stages of megakaryocyte differentiation. Blood. 2006;107(6):2303–10.PubMedCrossRef
14.
Cao Y, Cai J, Zhang S, Yuan N, Li X, Fang Y, et al. Loss of autophagy leads to failure in megakaryopoiesis, megakaryocyte differentiation, and thrombopoiesis in mice. Exp Hematol. 2015;43(6):488–94.PubMedCrossRef
15.
Shan NN, Dong LL, Zhang XM, Liu X, Li Y. Targeting autophagy as a potential therapeutic approach for immune thrombocytopenia therapy. Crit Rev Oncol Hematol. 2016;100:11–5.PubMedCrossRef
16.
Li J, Wang Z, Dai L, Cao L, Su J, Zhu M, et al. Effects of rapamycin combined with low dose prednisone in patients with chronic immune thrombocytopenia. Clin Dev Immunol. 2013;2013:548085.PubMedPubMedCentral
17.
Dong Z, Cui H. The autophagy-lysosomal pathways and their emerging roles in modulating proteostasis in tumors. Cells. 2018;8(1):4.PubMedCentralCrossRef
18.
Jimenez-Moreno N, Stathakos P, Caldwell MA, Lane JD. Induced pluripotent stem cell neuronal models for the study of autophagy pathways in human neurodegenerative disease. Cells. 2017;6(3):24.PubMedCentralCrossRef
19.
Mizushima N, Ohsumi Y, Yoshimori T. Autophagosome formation in mammalian cells. Cell Struct Funct. 2002;27(6):421–9.PubMedCrossRef
20.
21.
Song Q, Kumar A. An overview of autophagy and yeast pseudohyphal growth: integration of signaling pathways during nitrogen stress. Cells. 2012;1(3):263–83.PubMedPubMedCentralCrossRef
22.
Kobayashi S. Choose delicately and reuse adequately: the newly revealed process of autophagy. Biol Pharm Bull. 2015;38(8):1098–103.PubMedCrossRef
23.
Santambrogio L, Cuervo AM. Chasing the elusive mammalian microautophagy. Autophagy. 2011;7(6):652–4.PubMedCrossRef
24.
Bandyopadhyay U, Kaushik S, Varticovski L, Cuervo AM. The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane. Mol Cell Biol. 2008;28(18):5747–63.PubMedPubMedCentralCrossRef
25.
Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011;27:107–32.PubMedCrossRef
26.
27.
Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol. 2009;10(7):458–67.PubMedCrossRef
28.
Lamb CA, Yoshimori T, Tooze SA. The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol. 2013;14(12):759–74.PubMedCrossRef
29.
Russell RC, Yuan HX, Guan KL. Autophagy regulation by nutrient signaling. Cell Res. 2014;24(1):42–57.PubMedCrossRef
30.
Alers S, Loffler AS, Wesselborg S, Stork B. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol. 2012;32(1):2–11.PubMedPubMedCentralCrossRef
31.
Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122(6):927–39.PubMedCrossRef
32.
Liu L, Dong Z, Lei Q, Yang J, Hu H, Li Q, et al. Inactivation/deficiency of DHODH induces cell cycle arrest and programed cell death in melanoma. Oncotarget. 2017;8(68):112354–70.PubMedPubMedCentral
33.
34.
Warde N. Autoimmunity: the role of neutrophils in SLE: untangling the NET. Nat Rev Rheumatol. 2011;7(5):252.PubMedCrossRef
35.
Fuhler GM, Tyl MR, Olthof SG, Lyndsay Drayer A, Blom N, Vellenga E. Distinct roles of the mTOR components Rictor and Raptor in MO7e megakaryocytic cells. Eur J Haematol. 2009;83(3):235–45.PubMedCrossRef
36.
Drayer AL, Olthof SG, Vellenga E. Mammalian target of rapamycin is required for thrombopoietin-induced proliferation of megakaryocyte progenitors. Stem Cells. 2006;24(1):105–14.PubMedCrossRef
37.
Wirawan E, Vanden Berghe T, Lippens S, Agostinis P, Vandenabeele P. Autophagy: for better or for worse. Cell Res. 2012;22(1):43–61.PubMedCrossRef
38.
Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell. 2006;124(3):471–84.PubMedCrossRef
39.
Budovskaya YV, Stephan JS, Reggiori F, Klionsky DJ, Herman PK. The Ras/cAMP-dependent protein kinase signaling pathway regulates an early step of the autophagy process in Saccharomyces cerevisiae. J Biol Chem. 2004;279(20):20663–71.PubMedCrossRef
40.
Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z, Larrea M, et al. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol. 2007;9(2):218–24.PubMedCrossRef
41.
Hariharan N, Ikeda Y, Hong C, Alcendor RR, Usui S, Gao S, et al. Autophagy plays an essential role in mediating regression of hypertrophy during unloading of the heart. PLoS ONE. 2013;8(1):e51632.PubMedPubMedCentralCrossRef
42.
Suzuki K, Kirisako T, Kamada Y, Mizushima N, Noda T, Ohsumi Y. The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J. 2001;20(21):5971–81.PubMedPubMedCentralCrossRef
43.
Mizushima N, Noda T, Ohsumi Y. Apg16p is required for the function of the Apg12p–Apg5p conjugate in the yeast autophagy pathway. EMBO J. 1999;18(14):3888–96.PubMedPubMedCentralCrossRef
44.
45.
Kirisako T, Baba M, Ishihara N, Miyazawa K, Ohsumi M, Yoshimori T, et al. Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol. 1999;147(2):435–46.PubMedPubMedCentralCrossRef
46.
Shao Y, Gao Z, Feldman T, Jiang X. Stimulation of ATG12-ATG5 conjugation by ribonucleic acid. Autophagy. 2007;3(1):10–6.PubMedCrossRef
47.
Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H, German Aplastic Anemia Study G. Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood. 2003;101(4):1236–42.PubMedCrossRef
48.
Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, et al. Autophagosomes form at ER-mitochondria contact sites. Nature. 2013;495(7441):389–93.PubMedCrossRef
49.
Suzuki K, Kubota Y, Sekito T, Ohsumi Y. Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells. 2007;12(2):209–18.PubMedCrossRef
50.
Kirisako T, Ichimura Y, Okada H, Kabeya Y, Mizushima N, Yoshimori T, et al. The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. J Cell Biol. 2000;151(2):263–76.PubMedPubMedCentralCrossRef
51.
Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004;6(4):463–77.PubMedCrossRef
52.
Hirokawa N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science. 1998;279(5350):519–26.PubMedCrossRef
53.
Itakura E, Kishi-Itakura C, Mizushima N. The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell. 2012;151(6):1256–69.PubMedCrossRef
54.
Epple UD, Suriapranata I, Eskelinen EL, Thumm M. Aut5/Cvt17p, a putative lipase essential for disintegration of autophagic bodies inside the vacuole. J Bacteriol. 2001;183(20):5942–55.PubMedPubMedCentralCrossRef
55.
Teter SA, Eggerton KP, Scott SV, Kim J, Fischer AM, Klionsky DJ. Degradation of lipid vesicles in the yeast vacuole requires function of Cvt17, a putative lipase. J Biol Chem. 2001;276(3):2083–7.PubMedCrossRef
56.
Yang Z, Huang J, Geng J, Nair U, Klionsky DJ. Atg22 recycles amino acids to link the degradative and recycling functions of autophagy. Mol Biol Cell. 2006;17(12):5094–104.PubMedPubMedCentralCrossRef
57.
58.
59.
60.
Walsh CM, Edinger AL. The complex interplay between autophagy, apoptosis, and necrotic signals promotes T-cell homeostasis. Immunol Rev. 2010;236:95–109.PubMedPubMedCentralCrossRef
61.
Zhou XJ, Lu XL, Lv JC, Yang HZ, Qin LX, Zhao MH, et al. Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Ann Rheum Dis. 2011;70(7):1330–7.PubMedCrossRef
62.
Baumann I, Kolowos W, Voll RE, Manger B, Gaipl U, Neuhuber WL, et al. Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum. 2002;46(1):191–201.PubMedCrossRef
63.
Mizushima N, Klionsky DJ. Protein turnover via autophagy: implications for metabolism. Annu Rev Nutr. 2007;27:19–40.PubMedCrossRef
64.
Maiuri MC, Tasdemir E, Criollo A, Morselli E, Vicencio JM, Carnuccio R, et al. Control of autophagy by oncogenes and tumor suppressor genes. Cell Death Differ. 2009;16(1):87–93.PubMedCrossRef
65.
66.
67.
68.
Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008;456(7219):264–8.PubMedCrossRef
69.
International Consortium for Systemic Lupus Erythematosus G, Harley JB, Alarcon-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet. 2008;40(2):204–10.CrossRef
70.
Han JW, Zheng HF, Cui Y, Sun LD, Ye DQ, Hu Z, et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet. 2009;41(11):1234–7.PubMedCrossRef
71.
Gros F, Arnold J, Page N, Decossas M, Korganow AS, Martin T, et al. Macroautophagy is deregulated in murine and human lupus T lymphocytes. Autophagy. 2012;8(7):1113–23.PubMedPubMedCentralCrossRef
72.
Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010;69(1):20–8.PubMedCrossRef
73.
Henckaerts L, Cleynen I, Brinar M, John JM, Van Steen K, Rutgeerts P, et al. Genetic variation in the autophagy gene ULK1 and risk of Crohn’s disease. Inflamm Bowel Dis. 2011;17(6):1392–7.PubMedCrossRef
74.
Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev. 2013;93(1):327–58.PubMedCrossRef
75.
Li X, Cong H. Platelet-derived microparticles and the potential of glycoprotein IIb/IIIa antagonists in treating acute coronary syndrome. Tex Heart Inst J. 2009;36(2):134–9.PubMed
76.
Thushara RM, Hemshekhar M, Kemparaju K, Rangappa KS, Girish KS. Biologicals, platelet apoptosis and human diseases: an outlook. Crit Rev Oncol Hematol. 2015;93(3):149–58.PubMedCrossRef
77.
Ouseph MM, Huang Y, Banerjee M, Joshi S, MacDonald L, Zhong Y, et al. Autophagy is induced upon platelet activation and is essential for hemostasis and thrombosis. Blood. 2015;126(10):1224–33.PubMedPubMedCentralCrossRef
78.
Paul M, Hemshekhar M, Kemparaju K, Girish KS. Aggregation is impaired in starved platelets due to enhanced autophagy and cellular energy depletion. Platelets. 2018;26:1–11.CrossRef
79.
McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood. 2004;103(4):1364–9.PubMedCrossRef
80.
Lin X, Yin L, Gao R, Liu Q, Xu W, Jiang X, et al. The effects of panaxadiol saponins on megakaryocytic maturation and immune function in a mouse model of immune thrombocytopenia. Exp Hematol. 2015;43(5):364–73.PubMedCrossRef
81.
Kondo M, Wagers AJ, Manz MG, Prohaska SS, Scherer DC, Beilhack GF, et al. Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol. 2003;21:759–806.PubMedCrossRef
82.
Salemi S, Yousefi S, Constantinescu MA, Fey MF, Simon HU. Autophagy is required for self-renewal and differentiation of adult human stem cells. Cell Res. 2012;22(2):432–5.PubMedCrossRef
83.
84.
85.
Houwerzijl EJ, Pol HW, Blom NR, van der Want JJ, de Wolf JT, Vellenga E. Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy of mitochondria. Leukemia. 2009;23(5):886–91.PubMedCrossRef
86.
Chen M, Sandoval H, Wang J. Selective mitochondrial autophagy during erythroid maturation. Autophagy. 2008;4(7):926–8.PubMedCrossRef
87.
Mortensen M, Soilleux EJ, Djordjevic G, Tripp R, Lutteropp M, Sadighi-Akha E, et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med. 2011;208(3):455–67.PubMedPubMedCentralCrossRef
88.
Mortensen M, Ferguson DJ, Edelmann M, Kessler B, Morten KJ, Komatsu M, et al. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci USA. 2010;107(2):832–7.PubMedCrossRef
89.
Bluteau D, Lordier L, Di Stefano A, Chang Y, Raslova H, Debili N, et al. Regulation of megakaryocyte maturation and platelet formation. J Thromb Haemost. 2009;7(Suppl 1):227–34.PubMedCrossRef
90.
91.
Wang L, Li Y, Hou M. Idiopathic thrombocytopenic purpura and dysmegakaryocytopoiesis. Crit Rev Oncol Hematol. 2007;64(2):83–9.PubMedCrossRef
92.
Houwerzijl EJ, Blom NR, van der Want JJ, Esselink MT, Koornstra JJ, Smit JW, et al. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood. 2004;103(2):500–6.PubMedCrossRef
93.
Cooper N, Stasi R, Cunningham-Rundles S, Feuerstein MA, Leonard JP, Amadori S, et al. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol. 2004;125(2):232–9.PubMedCrossRef
94.
Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168–86.PubMedCrossRef
95.
Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, et al. Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol. 2005;25(3):1025–40.PubMedPubMedCentralCrossRef
96.
Reddy PS, Legault HM, Sypek JP, Collins MJ, Goad E, Goldman SJ, et al. Mapping similarities in mTOR pathway perturbations in mouse lupus nephritis models and human lupus nephritis. Arthritis Res Ther. 2008;10(6):R127.PubMedPubMedCentralCrossRef
97.
Lui SL, Tsang R, Chan KW, Zhang F, Tam S, Yung S, et al. Rapamycin attenuates the severity of established nephritis in lupus-prone NZB/W F1 mice. Nephrol Dial Transplant. 2008;23(9):2768–76.PubMedCrossRef
98.
Baldo P, Cecco S, Giacomin E, Lazzarini R, Ros B, Marastoni S. mTOR pathway and mTOR inhibitors as agents for cancer therapy. Curr Cancer Drug Targets. 2008;8(8):647–65.PubMedCrossRef
99.
Yap DY, Ma MK, Tang CS, Chan TM. Proliferation signal inhibitors in the treatment of lupus nephritis: preliminary experience. Nephrology (Carlton). 2012;17(8):676–80.PubMedCrossRef
100.
Chresta CM, Davies BR, Hickson I, Harding T, Cosulich S, Critchlow SE, et al. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res. 2010;70(1):288–98.PubMedCrossRef
101.
Zhou H, Hou Y, Liu X, Qiu J, Feng Q, Wang Y, et al. Low-dose decitabine promotes megakaryocyte maturation and platelet production in healthy controls and immune thrombocytopenia. Thromb Haemost. 2015;113(5):1021–34.PubMedCrossRef
102.
Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S, et al. Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science. 2004;304(5676):1500–2.PubMedCrossRef
103.
Liu Z, Mei T. Immune thrombocytopenia induces autophagy and suppresses apoptosis in megakaryocytes. Mol Med Rep. 2018;18(4):4016–22.PubMed
Metadata
Title
Megakaryocytic dysfunction in immune thrombocytopenia is linked to autophagy
Authors
Rui-jie Sun
Ning-ning Shan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0779-0

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