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Potentiated activation of VLA-4 and VLA-5 accelerates proplatelet-like formation

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Abstract

Fibronectin (FN) plays important roles in the proliferation, differentiation, and maintenance of megakaryocytic-lineage cells through FN receptors. However, substantial role of FN receptors and their functional assignment in proplatelet-like formation (PPF) of megakaryocytes are not yet fully understood. Herein, we investigated the effects of FN receptors on PPF using the CHRF-288 human megakaryoblastic cell line, which expresses VLA-4 and VLA-5 as FN receptors. FN and phorbol 12-myristate 13-acetate (PMA) were essential for inducing PPF in CHRF-288 cells. Blocking experiments using anti-β1-integrin monoclonal antibodies indicated that the adhesive interaction with FN via VLA-4 and VLA-5 were required for PPF. PPF induced by FN plus PMA was accelerated when CHRF-288 cells were enforced adhering to FN by TNIIIA2, a peptide derived from tenascin-C, which we recently found to induce β1-integrin activation. Adhesion to FN enhanced PMA-stimulated activation of extracellular signal-regulated protein kinase 1 (ERK1)/2 and enforced adhesion to FN via VLA-4 and VLA-5 by TNIIIA2-accelerated activation of ERK1/2 with FN plus PMA. However, c-Jun amino-terminal kinase 1 (JNK1), p38, and phosphoinositide-3 kinase (PI3K)/Akt were not stimulated by FN plus PMA, even with TNIIIA2. Thus, the enhanced activation of ERK1/2 by FN, PMA plus TNIIIA2 was responsible for acceleration of PPF with FN plus PMA.

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References

  1. Williams DA (1994) Molecular analysis of the hematopoietic microenvironment. Pediatr Res 36(5):557–560

    Article  PubMed  CAS  Google Scholar 

  2. Coulombel L, Vuillet M, Leroy C, Tchernia G (1998) Lineage- and stage-specific adhesion of human hematopoietic progenitor cells to extracellular matrices from marrow fibroblasts. Blood 71(2):329–334

    Google Scholar 

  3. Williams DA, Rios M, Stephens C, Patel VP (1991) Fibronectin and VLA-4 in haematopoietic stem cell–microenvironment interactions. Nature 352(6334):438–441

    Article  PubMed  CAS  Google Scholar 

  4. Vuillet-Gaugher MH, Breton-Gorius J, Vainchenker W, Guichard J, Leroy C, Tchernia G, Coulombel L (1990) Loss of attachment to fibronectin with terminal human erythroid differentiation. Blood 75(4):865–873

    Google Scholar 

  5. Weistein R, Riordan MA, Wenc K, Krecako S, Zhou M, Dainiak N (1989) Dual role of fibronectin in hematopoietic differentiation. Blood 73(1):111–116

    Google Scholar 

  6. Eshgi S, Vogelezang MG, Hynes RO, Griffith LG, Lodish HF (2007) Alpha4beta1 integrin and erythropoietin mediate temporally distinct steps in erythropoiesis: integrins in red cell development. J Cell Biol 177(5):871–880

    Article  Google Scholar 

  7. Dao MA, Creer MH, Nolta JA, Verfaillie CM (2007) Biology of umbilical cord blood progenitors in bone marrow niches. Blood 110(1):74–81

    Article  PubMed  CAS  Google Scholar 

  8. Fox NE, Kaushansky K (2005) Engagement of integrin alpha4beta1 enhances thrombopoietin-induced megakaryopoiesis. Exp Hematol 33(1):94–99

    Article  PubMed  CAS  Google Scholar 

  9. Han P, Guo X, Story C (2004) Role of beta(1)-integrins and their associated tetraspanin molecules in fibronectin-enhanced megakaryopoiesis. Cytotherapy 6(5):465–475

    Article  PubMed  CAS  Google Scholar 

  10. Mossuz P, Schweitzer A, Molla A, Berthier R (1997) Expression and function of receptors for extracellular matrix molecules in the differentiation of human megakaryocytes in vitro. Br J Haematol 98(4):819–827

    Article  PubMed  CAS  Google Scholar 

  11. Fukai F, Takahashi H, Habu Y, Kubushiro N, Katayama T (1996) Fibronectin harbors anticell adhesive activity. Biochem Biophys Res Commun 220(2):394–398

    Article  PubMed  CAS  Google Scholar 

  12. Fukai F, Hasebe S, Ueki M, Mutoh M, Ohgi C, Takahashi H, Takeda K, Katayama T (1997) Identification of the anti-adhesive site buried within the heparin-binding domain of fibronectin. J Biochem 121(2):189–192

    PubMed  CAS  Google Scholar 

  13. Kamiya S, Kato R, Wakabayashi M, Tohyama T, Enami I, Ueki M, Yajima H, Ishii T, Nakamura H, Katayama T, Takagi J, Fukai F (2002) Fibronectin peptides derived from two distinct regions stimulate adipocyte differentiation by preventing fibronectin matrix assembly. Biochem 41(9):3270–3277

    Article  CAS  Google Scholar 

  14. Erickson HP (1993) Tenascin-C, tenascin-R and tenascin-X: a family of talented proteins in search of functions. Curr Opin Cell Biol 5(5):869–876

    Article  PubMed  CAS  Google Scholar 

  15. Fischer D, Brown-Ludi M, Schulthess T, Chiquet-Ehrismann R (1997) Concerted action of tenascin-C domains in cell adhesion, anti-adhesion and promotion of neurite outgrowth. J Cell Sci 110(Pt13):1513–1522

    PubMed  CAS  Google Scholar 

  16. Saito Y, Imazeki H, Miura S, Yoshimura T, Okutsu H, Harada Y, Ohwaki T, Nagao O, Kamiya S, Hayashi R, Kodama H, Handa H, Yoshida T, Fukai F (2007) A peptide derived from tenascin-C induces beta1 integrin activation through syndecan-4. J Biol Chem 282(48):34929–34937

    Article  PubMed  CAS  Google Scholar 

  17. Tanaka R, Owaki T, Kamiya S, Matsunaga T, Shimoda K, Kodama H, Hayashi R, Abe T, Harada YP, Shimonaka M, Yajima H, Terada H, Fukai F (2009) VLA-5-mediated adhesion to fibronectin accelerates hemin-stimulated erythroid differentiation of K562 cells through induction of VLA-4 expression. J Biol Chem 284(30):19817–19825

    Article  PubMed  CAS  Google Scholar 

  18. Saito Y, Shiota Y, Nishisaka M, Owaki T, Shimamura M, Fukai F (2008) Inhibition of angiogenesis by a tenascin-c peptide which is capable of activating beta1-integrins. Biol Pharm Bull 31(5):1003–1007

    Article  PubMed  CAS  Google Scholar 

  19. Watanabe K, Takahashi H, Habu Y, Kamiya-Kubushiro N, Kamiya S, Nakamura H, Yajima H, Ishii T, Katayama T, Miyazaki M, Fukai F (2000) Interaction with heparin and matrix metalloproteinase 2 cleavage expose a cryptic anti-adhesive site of fibronectin. Biochem 39(24):7138–7144

    Article  CAS  Google Scholar 

  20. Park JI, Choi HS, Jeong JS, Han JY, Kim IH (2001) Involvement of p38 kinase in hydroxyurea-induced differentiation of K562 cells. Cell Growth Diff 12(9):481–486

    PubMed  CAS  Google Scholar 

  21. Di Pietro R, di Giacomo V, Caravatta L, Sancillio S, Rana RA, Cataldi A (2007) Cyclic nucleotide response element binding (CREB) protein activation is involved in K562 erythroleukemia cells differentiation. J Cell Biochem 100(4):1070–1079

    Article  PubMed  Google Scholar 

  22. Zutter MM, Painter AD, Yang X (1999) The megakaryocyte/platelet-specific enhancer of the alpha2beta1 integrin gene: two tandem AP1 sites and the mitogen-activated protein kinase signaling cascade. Blood 93(5):1600–1611

    PubMed  CAS  Google Scholar 

  23. Jiang F, Jia Y, Cohen I (2001) Fibronectin- and protein kinase C-mediated activation of ERK/MAPK are essential for proplateletlike formation. Blood 99(10):3579–3584

    Article  Google Scholar 

  24. Takagi J, Isobe T, Takada Y, Saito Y (1997) Structual interlock between ligand-binding site and stalk-like region of beta1 integrin revealed by a monoclonal antibody recognizing conformation-dependent epitope. J Biochem 121(5):914–921

    Article  PubMed  CAS  Google Scholar 

  25. Moursi AM, Globus RK, Damsky CH (1997) Interactions between integrin receptors and fibronectin are required for calvarial osteoblast differentiation in vitro. J Cell Sci 110(Pt18):2187–2196

    PubMed  CAS  Google Scholar 

  26. Kalina U, Koschmieder S, Hofmann WK, Wanger S, Kauschat D, Hoelzer D, Ottmann OG (2001) Transforming growth factor-beta1 interferes with thrombopoietin-induced signal transduction in megakaryoblastic and erythroleukemic cells. Exp Hematol 29(5):602–608

    Article  PubMed  CAS  Google Scholar 

  27. Miyazaki R, Ogata H, Kobayashi Y (2001) Requirement of thrombopoietin-induced activation of ERK for megakaryocyte differentiation and of p38 for erythroid differentiation. Ann Hematol 80(5):284–291

    Article  PubMed  CAS  Google Scholar 

  28. Mazharian A, Watson SP, Séverin S (2009) Clinical role for ERK1/2 in bone marrow and fetal liver-derived primary megakaryocyte differentiation, motility, and proplatelet formation. Exp Hematol 37(10):1238–1249

    Article  PubMed  CAS  Google Scholar 

  29. Jin UH, Ha KT, Kim KW, Chang YC, Lee YC, Ko JH, Kim CH (2008) Membrane type sialidase inhibits the megakaryocytic differentiation of human leukemia K562 cells. Biochem Biophys Acta 1780(5):757–763

    Article  PubMed  CAS  Google Scholar 

  30. Eriksson M, Arminen L, Karjalainen-Lindsberg ML, Leppa S (2005) AP-1 regulates alpha2beta1 integrin expression by ERK-dependent signals during megakaryocytic differentiation of K562 cells. Exp Cell Res 304(1):175–186

    Article  PubMed  CAS  Google Scholar 

  31. Jacquel A, Herrant M, Defamie V, Belhacene N, Colosetti P, Marchetti S, Legros L, Deckert M, Mari B, Cassuto JP, Hofman P, Auberger P (2006) A survey of the signaling pathways involved in megakaryocytic differentiation of the human K562 leukemia cell line by molecular and c-DNA array analysis. Oncogene 25(5):781–794

    Article  PubMed  CAS  Google Scholar 

  32. Wang JP, Park IW, Groopman JE (2000) Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: role of phosphoinositide-3 kinase and protein kinase C. Blood 95(8):2505–2513

    PubMed  CAS  Google Scholar 

  33. Kanasaki H, Fukunaga K, Takahashi K, Miyazaki K, Miyamoto E (2000) Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells. Biol Reprod 62(6):1486–1494

    Article  PubMed  CAS  Google Scholar 

  34. Yue TL, Wang C, Gu JL, Ma XL, Kumar S, Lee JC, Fuerstein GZ, Thomas H, Maleeff B, Ohlstein EH (2000) Inhibition of extracellular signal-regulated kinase enhances ischemia/reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ Res 86(6):692–699

    Article  PubMed  CAS  Google Scholar 

  35. Ni H, Li A, Simonsen N, Wilkins JA (1998) Integrin activation by dithiothreitol or Mn2+ induces a ligand-occupied conformation and exposure of a novel NH2-terminal regulatory site on the beta1 integrin chain. J Biol Chem 273(14):7981–7987

    Article  PubMed  CAS  Google Scholar 

  36. Ogawa M (1993) Differentiation and proliferation of hematopoietic stem cells. Blood 81(11):2844–2883

    PubMed  CAS  Google Scholar 

  37. Behnke O (1969) An electron microscope study of the rat megakaryocyte. II. Some aspects of platelet release and microtubles. J Ultrastruct Res 26(1):111–129

    Article  PubMed  CAS  Google Scholar 

  38. Lichtman MA, Chamberlain JK, Simon W, Santillo PA (1978) Parasinusoidal location of megakaryocytes in marrow: a determinant of platelet release. Am J Hematol 4(4):303–312

    Article  PubMed  CAS  Google Scholar 

  39. Radley JM, Scurfield G (1980) The mechanism of platelet release. Blood 56(6):996–999

    PubMed  CAS  Google Scholar 

  40. Scurfield G, Radley JM (1981) Aspects of platelet formation and release. Am J Hematol 10(3):285–296

    Article  PubMed  CAS  Google Scholar 

  41. Becker RP, De Bruyn PPH (1976) The transmural passage of blood cells into myeloid sinusoids and the entry of platelets into the sinusoidal circulation; a scanning electron microscopic investigation. Am J Anat 145(2):183–205

    Article  PubMed  CAS  Google Scholar 

  42. Junt T, Schulze H, Chen Z, Massberg S, Goerge T, Krueger A, Wagner DD, Graf T Jr, Italiano JE, Shivdasani RA, von Andrian UH (2007) Dynamic visualization of thrombopoiesis within bone marrow. Sci 317(5845):1767–1770

    Article  CAS  Google Scholar 

  43. Debil N, Wendling F, Katz A, Guichard J, Breton-Gorius J, Hunt P, Vainchenker W (1995) The Mpl-ligand or thrombopoietin or megakaryocyte growth and differentiative factor has both direct proliferative and differentiative activities on human megakaryocyte progenitors. Blood 86(7):2516–2525

    Google Scholar 

  44. Choi ES, Nichol JL, Hokom MM, Hornkohl AC, Hunt P (1995) Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional. Blood 85(2):402–413

    PubMed  CAS  Google Scholar 

  45. Hagiwara T, Kodama I, Horie K, Kato T, Miyazaki H (1998) Proliferative properties of human umbilical cord blood megakaryocyte progenitor cells to human thrombopoietin. Exp Hematol 26(3):228–235

    PubMed  CAS  Google Scholar 

  46. Lecine P, Blank V, Shivdasani R (1998) Characterization of the hematopoietic transcription factor NF-E2 in primary murine megakaryocytes. J Biol Chem 273(13):7572–7578

    Article  PubMed  CAS  Google Scholar 

  47. Leven RM, Yee MK (1987) Megakaryocyte morphogenesis stimulated in vitro by whole and partially fractionated thrombocytopenic plasma: a model system for the study of platelet formation. Blood 69(4):1046–1052

    PubMed  CAS  Google Scholar 

  48. Hunt P, Hokom MM, Wiemann B, Leven RM, Arakawa T (1993) Megakaryocyte proplatelet-like process formation in vitro is inhibited by serum prothrombin, a process which is blocked by matrix-bound glycosaminoglycans. Exp Hematol 21(2):372–381

    PubMed  CAS  Google Scholar 

  49. Hunt P, Hokom MM, Hornkohl A, Wiemann B, Rohde MF, Arakawa T (1993) The effect of the platelet-derived glycosaminoglycan serglycin on in vitro proplatelet-like process formation. Exp Hematol 21(9):1295–1304

    PubMed  CAS  Google Scholar 

  50. Cramer EM, Norol E, Guichard J, Breton-Gorius J, Vainchenker M, Debili N (1997) Ultrastructure of platelet formation by human megakaryocytes cultured with Mpl ligand. Blood 89(7):2336–2346

    PubMed  CAS  Google Scholar 

  51. Laplante AF, Germain L, Auger FA, Moulin V (2001) Mechanisms of wound reepithelialization: hints from a tissue-engineered reconstructed skin to long-standing questions. FASEB J 15(13):2377–2389

    Article  PubMed  CAS  Google Scholar 

  52. Tözüm TF, Demiralp B (2003) Platelet-rich plasma: a promising innovation in dentistry. J Can Dent Assoc 69(10):664–664h

    PubMed  Google Scholar 

  53. Matsunaga T, Tanaka I, Kobune M, Kawano Y, Tanaka M, Kuribayashi K, Iyama S, Sato T, Sato Y, Takimoto R, Takayama T, Kato J, Ninomiya T, Hamada H, Niitsu Y (2006) Ex vivo large-scale generation of human platelets from cord blood CD34+ cells. Stem cells 24(12):2877–2887

    Article  PubMed  CAS  Google Scholar 

  54. Rojnuckarin P, Drachman JG, Kaushansky K (1999) Thrombopoietin-induced activation of the mitogen-activated protein kinase (MAPK) pathway in normal megakaryocytes: role in endomitosis. Blood 94(4):1273–1282

    PubMed  CAS  Google Scholar 

  55. Mackie EJ, Halfter W, Liverani D (1988) Induction of tenascin in healing wounds. J Cell Biol 107(6Pt2):2757

    Article  PubMed  CAS  Google Scholar 

  56. Chiquet-Ehrismann R, Mackie EJ, Pearson CA, Sakakura T (1986) Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell 47(1):131–139

    Article  PubMed  CAS  Google Scholar 

  57. Chilosi M, Lestani M, Benedetti A, Montagna L, Pedron S, Scarpa A, Menestrina F, Hirohashi S, Pizzolo G, Semenzato G (1993) Constitutive expression of tenascin in T-dependent zones of human lymphoid tissues. Am J Pathol 143(5):1348–1355

    PubMed  CAS  Google Scholar 

  58. Ocklind G, Talts J, Fassler R, Mattsson A, Ekblom P (1993) Expression of tenascin in developing and adult mouse lymphoid organs. J Histochem Cytochem 41(8):1163–1169

    Article  PubMed  CAS  Google Scholar 

  59. Klein G, Beck S, Müller CA (1993) Tenascin is a cytoadhesive extracellular matrix component of the human hematopoietic microenvironment. J Cell Biol 123(4):1027–1035

    Article  PubMed  CAS  Google Scholar 

  60. Seki M, Kameoka J, Takahashi S, Harigae H, Yanai N, Obinata M, Sasaki T (2006) Identification of tenascin-C as a key molecule determination stromal cell-dependent erythropoiesis. Exp Hematol 34(4):519–527

    Article  PubMed  CAS  Google Scholar 

  61. Ohta M, Sakai T, Saga Y, Aizawa S, Saito M (1998) Suppression of hematopoietic activity in tenascin-C-deficient mice. Blood 91(11):4074–4083

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Grants-in-Aid for Scientific Research grant to T.M, F.F, Y.K., and K.S.

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Authors and Affiliations

  1. Department of Gastroenterology and Hematology, Miyazaki University, 5200 Kihara, Kiyotake,, Miyazaki, 889-1692, Japan

    Takuya Matsunaga, Takuro Kameda, Kotaro Shide, Haruko Shimoda, Eri Torii, Ayako Kamiunten, Masaaki Sekine, Shojirou Yamamoto, Tomonori Hidaka, Yoko Kubuki & Kazuya Shimoda

  2. Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, , Noda-Shi, Chiba, 278-8510, Japan

    Fumio Fukai

  3. Division of Endocrinology and Metabolism, Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, , Kita-gun, Kagawa, 761-0793, Japan

    Takuya Matsunaga, Shigeyuki Yokokura, Makiko Uemura, Akihito Matsuoka, Fusako Waki, Kensuke Matsumoto, Nobuhiro Kanaji, Tomoya Ishii, Osamu Imataki, Hiroaki Dobashi & Shuji Bandoh

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Correspondence to Takuya Matsunaga.

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Supplementary Figure 1

Expression of fibronectin receptors and Syndecan-4 in CHRF-288 cells. (A) Flow cytometric (FACS) analyses of fibronectin receptor β1-integrins on CHRF-288 cells. FACS analyses were performed using the normal IgG or anti-β1-integrins mAb, (a) normal IgG (negative control), (b) anti-α3-integrin mAb, (c) anti-α4-integrin mAb, (d) anti-α5-integrin mAb, (e) anti-αV-integrin mAb, and (f) anti-β1-integrin mAb, as described in “Materials and methods”. Data shown are representative of three individual experiments. (B) FACS analyses of Syndecan-4 in CHRF-288 cells. FACS analyses were performed using the FITC-labeled normal IgG (┅┅┅) or FITC-labeled anti-Syndecan-4 mAb (━━━), as described in “Materials and methods”. Data shown are representative of three individual experiments. (JPEG 282 kb)

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Matsunaga, T., Fukai, F., Kameda, T. et al. Potentiated activation of VLA-4 and VLA-5 accelerates proplatelet-like formation. Ann Hematol 91, 1633–1643 (2012). https://doi.org/10.1007/s00277-012-1498-y

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