Prominent role of TGF-β1 in thrombopoietin-induced myelofibrosis in mice

Blood - Tập 100 - Trang 3495-3503 - 2002
Hédia Chagraoui, Emiko Komura, Micheline Tulliez, Stéphane Giraudier, William Vainchenker, Françoise Wendling

Tóm tắt

Several studies suggest an implication of transforming growth factor-β1 (TGF-β1) in the promotion of myelofibrosis associated with hematopoietic malignancies, but the involvement of this cytokine is not fully investigated. To test directly the impact of TGF-β1 in the pathogenesis of myelofibrosis, bone marrow stem cells from homozygous TGF-β1 null (TGF-β1−/−) and wild-type (WT) littermates were infected with a retrovirus encoding the murine thrombopoietin (TPO) protein and engrafted into lethally irradiated wild-type hosts for long-term reconstitution. Over the 4 months of follow-up, TPO levels in plasma were markedly elevated in both groups of mice, and animals typically developed a myeloproliferative syndrome characterized by thrombocytosis, leukocytosis, splenomegaly, increased numbers of progenitors in blood, and extramedullary hematopoiesis. Severe fibrosis was observed in spleen and marrow from all the mice engrafted with WT cells. In contrast, none of the mice repopulated with TGF-β1−/− cells (chimerism > 70%) showed deposition of reticulin fibers at any time during the follow-up. In accordance with the development of fibrosis, latent TGF-β1 levels in plasma and extracellular fluid of the spleen from mice engrafted with WT cells were increased 6-fold and 4-fold, respectively, over levels found in normal hosts, whereas no increase over baseline levels could be demonstrated in animals undergoing transplantation with TGF-β1−/− cells. These data provide evidence that TGF-β1 produced by hematopoietic cells is pivotal for the pathogenesis of myelofibrosis that develops in mice with TPO overexpression.

Tài liệu tham khảo

Anderson, 1997, Myelodysplasia and myeloproliferative disorders., Curr Opin Hematol., 4, 261, 10.1097/00062752-199704040-00007 Reilly, 1998, Pathogenesis and management of idiopathic myelofibrosis., Baillieres Clin Haematol., 4, 751, 10.1016/S0950-3536(98)80037-1 Barosi, 1999, Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines., J Clin Oncol., 17, 2954, 10.1200/JCO.1999.17.9.2954 Jacobson, 1978, Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis., Blood., 51, 189, 10.1182/blood.V51.2.189.bloodjournal512189 Greenberg, 1987, Cytogenetics of bone marrow fibroblastic cells in idiopathic chronic myelofibrosis., Br J Haematol., 66, 487, 10.1111/j.1365-2141.1987.tb01332.x Thiele, 1989, Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/sclerosis (agnogenic myeloid metaplasia): correlations between clinical and morphological features., Anat Histopathol., 415, 191 Martyre, 1995, TGF-β and megakaryocytes in the pathogenesis of myelofibrosis in myeloproliferative disorders., Leuk Lymphoma., 20, 39, 10.3109/10428199509054751 Martyre, 1997, Elevated levels of basic fibroblast growth factor in megakaryocytes and platelets from patients with idiopathic myelofibrosis., Br J Haematol., 97, 441, 10.1046/j.1365-2141.1997.292671.x Rameshwar, 1998, Systemic transforming growth factor-β in patients with bone marrow fibrosis: pathophysiological implications., Am J Hematol., 59, 133, 10.1002/(SICI)1096-8652(199810)59:2<133::AID-AJH6>3.0.CO;2-Z Le Bousse-Kerdiles, 1999, Dual implication of fibrogenic cytokines in the pathogenesis of fibrosis and myeloproliferation in myeloid metaplasia with myelofibrosis., Ann Hematol., 78, 437, 10.1007/s002770050595 Roberts, 1986, Transforming growth factor type β: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro., Proc Natl Acad Sci U S A., 83, 4167, 10.1073/pnas.83.12.4167 Kimura, 1989, Transforming growth factor-β regulates growth as well as collagen and fibronectin synthesis of human marrow fibroblasts., Br J Haematol., 72, 489, 10.1111/j.1365-2141.1989.tb04310.x Massagué, 1990, The transforming growth factor-β family., Annu Rev Cell Biol., 6, 597, 10.1146/annurev.cb.06.110190.003121 Ignotz, 1987, Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-β., J Biol Chem., 262, 6443, 10.1016/S0021-9258(18)48258-0 Mervin, 1990, Transforming growth factor-β modulates extracellular matrix organisation and cell-cell junctional complex formation during in vitro angiogenesis., J Cell Physiol., 142, 117, 10.1002/jcp.1041420115 Castro-Malaspina, 1984, Pathogenesis of myelofibrosis: role of ineffective megakaryopoiesis and megakaryocyte components., Prog Clin Biol Res., 154, 427 Terui, 1990, The production of transforming growth factor-β in acute megakaryoblastic leukemia and its possible implications in myelofibrosis., Blood., 75, 1540, 10.1182/blood.V75.7.1540.1540 Reilly, 1993, Characterization of an acute micromegakaryocytic leukemia: evidence for the pathogenesis of myelofibrosis., Br J Haematol., 83, 58, 10.1111/j.1365-2141.1993.tb04631.x Ulich, 1996, Systemic hematologic effects of PEG-rHuMGDF- induced megakaryocyte hyperplasia in mice., Blood., 87, 5006, 10.1182/blood.V87.12.5006.bloodjournal87125006 Yanagida, 1997, The role of transforming growth factor-β in PEG-rHuMGDF-induced reversible myelofibrosis in rats., Br J Haematol., 99, 739, 10.1046/j.1365-2141.1997.4843288.x Yan, 1995, Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice., Blood., 86, 4025, 10.1182/blood.V86.11.4025.bloodjournal86114025 Yan, 1996, A model of myelofibrosis and osteosclerosis in mice induced by overexpressing thrombopoietin (mpl ligand): reversal of disease by bone marrow transplantation., Blood., 88, 402, 10.1182/blood.V88.2.402.bloodjournal882402 Villeval, 1997, High thrombopoietin production by hemopoietic cells induces a fatal myeloproliferative syndrome in mice., Blood., 90, 4369, 10.1182/blood.V90.11.4369 Shull, 1992, Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease., Nature., 359, 693, 10.1038/359693a0 Kallapur, 1999, Strain dependency of TGF-β1 function during embryogenesis., Mol Reprod Dev., 52, 341, 10.1002/(SICI)1098-2795(199904)52:4<341::AID-MRD2>3.0.CO;2-N Pear, 1998, Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow., Blood., 92, 3780, 10.1182/blood.V92.10.3780 Keller, 1990, Transforming growth factor β directly regulates primitive murine hematopoietic cell proliferation., Blood., 75, 596, 10.1182/blood.V75.3.596.596 Sitnicka, 1996, Transforming growth factor β1 directly and reversibly inhibits the initial cell divisions of long term repopulating hematopoietic stem cells., Blood., 88, 82, 10.1182/blood.V88.1.82.82 Ishibashi, 1987, Type β transforming growth factor is a potent inhibitor of megakaryocytopoiesis in vitro., Blood., 69, 1737, 10.1182/blood.V69.6.1737.1737 Kuter, 1992, Transforming growth factor β inhibits megakaryocytic growth and endomitosis., Blood., 79, 619, 10.1182/blood.V79.3.619.619 Keller, 1991, Stimulation of granulopoiesis by transforming growth factor β: synergy with granulocyte/macrophage-colony stimulating factor., Proc Natl Acad Sci U S A., 88, 7190, 10.1073/pnas.88.16.7190 Border, 1994, Transforming growth factor β in tissue fibrosis., N Engl J Med., 331, 1286, 10.1056/NEJM199411103311907 Kulkarni, 1993, Transforming growth factor-β 1 null mutation in mice causes excessive inflammatory response and early death., Proc Natl Acad Sci U S A., 90, 770, 10.1073/pnas.90.2.770 Yan, 1994, Overexpression of PDGF-B in murine hematopoietic cells induces a lethal myeloproliferative syndrome in vivo., Oncogene., 9, 163 Bonyadi, 1997, Mapping of a major genetic modifier of embryonic lethality in TGFβ1 knockout mice., Nat Genet., 15, 207, 10.1038/ng0297-207 Yaswen, 1996, Autoimmune manifestations in the transforming growth factor-β1 knockout mouse., Blood., 87, 1439, 10.1182/blood.V87.4.1439.bloodjournal8741439 Burns, 1993, Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells., Proc Natl Acad Sci U S A., 90, 8033, 10.1073/pnas.90.17.8033 Rebel, 1999, One-day ex vivo culture allows effective gene transfer into human nonobese diabetic/severe combined immune-deficient repopulating cells using high-titer vesicular stomatitis virus G protein pseudotyped retrovirus., Blood., 93, 2217, 10.1182/blood.V93.7.2217 Joyce, 1990, Transforming growth factor-β and the initiation of chondrogenesis and osteogenesis in the rat femur., J Cell Biol., 110, 2195, 10.1083/jcb.110.6.2195 Centrella, 1994, Transforming growth factor-β gene family members and bone., Endocr Rev., 15, 27 Takai, 1998, Transforming growth factor-β stimulates the production of osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal cells., J Biol Chem., 273, 27091, 10.1074/jbc.273.42.27091 Frey, 1998, Adenovector-mediated expression of human thrombopoietin cDNA in immune-compromised mice: insights into the pathophysiology of osteomyelofibrosis., J Immunol., 160, 691, 10.4049/jimmunol.160.2.691 Crawford, 1998, Thrombospondin-1 is a major activator of TGF-β1 in vivo., Cell., 93, 1159, 10.1016/S0092-8674(00)81460-9 Munger, 1999, The integrin αvβ6 binds and activates latent TGFβ1: a mechanism for regulating pulmonary inflammation and fibrosis., Cell., 96, 319, 10.1016/S0092-8674(00)80545-0 Lee, 2001, Interleukin-13 induces tissue fibrosis by selectively stimulating and activating growth factor β1., J Exp Med., 194, 809, 10.1084/jem.194.6.809
Thông tin
Thông tin xuất bản

Blood

Tập 100

3495-3503

Thông tin tác giả