纤维连接蛋白及重组FN肝素结合域多肽对血小板减少内毒素血症小鼠治疗作用的初步研究
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摘要
纤维连接蛋白(Fibronectin,FN)是细胞外基质的重要成份,为一种具有多种功能的糖蛋白大分子,能与肝素、胶原、纤维蛋白以及整合素受体结合,参与细胞的粘附、迁移、止血、损伤修复等过程、在抗感染、维持微血管的完整性等方面具有重要作用。大量研究表明血浆FN水平的测定对感染的预后评价具有重要意义。严重感染,如败血症患者血浆FN水平明显且急剧降低,给其补充富含FN的冷沉淀素,则在患者血浆FN恢复的同时,伴有心肺功能的改善及内毒素血症的控制,死亡率也随之下降。我们前期工作表明FN能降低半乳糖胺敏化内毒素小鼠的死亡率,有助于改善内毒素血症的病情及预后。重组FN肝素结合域多肽(rhFNHN-29)位于FN的N端,由五个I型的同源结构组成,该结构域的分子量为29kDa,由237个氨基酸组成,可与肝素结合。应用FN肝素结合域多肽治疗鼠内毒素血症和血小板减少模型,目前国内外尚未见报道。在本研究中,为了更真实地反映血液病患者常见的感染和出血并存的情况,我们设计了血小板减少内毒素血症小鼠模型,观察FN及rhFNHN-29对其疗效作用,并初步探讨其作用机制,为FN及rhFNHN-29的临床应用提供理论及实验依据。
本文的研究内容主要包括:
1.血小板减少内毒素血症小鼠模型的构建
每只小鼠腹腔注射血小板抗血清(APS)100μl,30分钟后腹腔注射500μl含内毒素脂多糖(LPS)300μg加半乳糖胺(GalN)10mg的混合液。通过血小板监测和72小时后小鼠的肝脏组织病理形态学观察验证模型是否成功构建。
2.FN及rhFNHN-29对血小板减少内毒素血症小鼠的作用,并初步探讨其作用机制
Fibronectin is known to be a large multifunctional glycoprotein with binding sites for many substances, including heparin, collagen, fibrinogen, fibrin and integrin. It is involved in a variety of cellular processes, such as cell migration, adhesion, hemostasis and tissue repair. And it plays an important role in maintaining the integrity of blood capillary and anti-infection. Many clinical studies suggested that plasma fibronectin concentration might be a prognostic index for endotoxemia. Clinical trails also suggested that reversal of plasma FN deficiency by infusion of FN-rich cryoprecipitate might result in a marked improvement of cardiopulmonary function in the endotoxemia patients. Our previous studies indicated that plasma FN could prevent hepatic failure induced by endotoxin in mice. Recombinant heparin-binding domain of FN is located at its amino-terminal, consisting of 5 typeⅠrepeats with 237 amino acids. There had been few reports in the world that the heparin-binding domain in intact FN molecular structure could be used in the treatment of endotoxemia with thrombocytopenia in mice. In the studies, we designed the model of endotoxemia with thrombocytopenia for actual reproduction of the concomitance state of endotoxemia and thrombocytopenia in hematologic disease, and investigate the therapeutical effect of FN and rhFNHN-29 on this state.
The subjects of this thesis were focused on the following aspects:
1. The construction of the model of endotoxemia with thrombocytopenia in mice
本文的研究内容主要包括:
1.血小板减少内毒素血症小鼠模型的构建
每只小鼠腹腔注射血小板抗血清(APS)100μl,30分钟后腹腔注射500μl含内毒素脂多糖(LPS)300μg加半乳糖胺(GalN)10mg的混合液。通过血小板监测和72小时后小鼠的肝脏组织病理形态学观察验证模型是否成功构建。
2.FN及rhFNHN-29对血小板减少内毒素血症小鼠的作用,并初步探讨其作用机制
Fibronectin is known to be a large multifunctional glycoprotein with binding sites for many substances, including heparin, collagen, fibrinogen, fibrin and integrin. It is involved in a variety of cellular processes, such as cell migration, adhesion, hemostasis and tissue repair. And it plays an important role in maintaining the integrity of blood capillary and anti-infection. Many clinical studies suggested that plasma fibronectin concentration might be a prognostic index for endotoxemia. Clinical trails also suggested that reversal of plasma FN deficiency by infusion of FN-rich cryoprecipitate might result in a marked improvement of cardiopulmonary function in the endotoxemia patients. Our previous studies indicated that plasma FN could prevent hepatic failure induced by endotoxin in mice. Recombinant heparin-binding domain of FN is located at its amino-terminal, consisting of 5 typeⅠrepeats with 237 amino acids. There had been few reports in the world that the heparin-binding domain in intact FN molecular structure could be used in the treatment of endotoxemia with thrombocytopenia in mice. In the studies, we designed the model of endotoxemia with thrombocytopenia for actual reproduction of the concomitance state of endotoxemia and thrombocytopenia in hematologic disease, and investigate the therapeutical effect of FN and rhFNHN-29 on this state.
The subjects of this thesis were focused on the following aspects:
1. The construction of the model of endotoxemia with thrombocytopenia in mice
引文
1. Debra J,Romberger.Fibronectin[J].Biochem.cellboil.(1997)29,939-943.
2. Ruiz G, Veiga J, Luisa Gomez-Lus,et al. Plasmatic concentrations of fibronectin as marker of clinical course among septic patients. Enferm Infecc Microbiol Clin. 2001 Mar;19(3):93-8.
3.Saba TM, F.A.Blumenstock, WA Scovill, et al. Cryoprecipitate reversal of opsonic α2-surface binding glycoprotein deficiency in septic surgical and trauma patients. Science 1978,201:622-624.
4.Saba TM, F.A.Blumenstock, DM Shah, et al. Reversal of fibronectin and opsonic deficiency in patients: a controlled study. Ann.surg 1984,199:87-96.
5.吴勇, 陈元仲,吕联煌等. 纤维连接蛋白对内毒素血症小鼠保护作用的实验研究.中国病理生理杂志,2003,(06):799-802.
6.Yong Wu, Yuan-zhong Chen, Hui-fang Huang,et al. Recombinant fibronectin polypeptide antagonizes hepaticfailure induced by endotoxin in mice, Acta Pharmacol Sin 2004 Jun; 25 (6): 783-788
7.Pankov R, Yamada KM. Fibronectin at a glance. J Cell Sci. 2002 Oct 15;115(Pt 20):3861-3.
8.Leist M,Gantner F,Bohlinger I,et al.Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models.Am J Pathol.1995,146(5):1220-1234
9.杨宇飞,周蔼祥等. 免疫性血小板减少性紫癜动物模型的建立. 中华血液学杂志.1994,15:160-161.
10.Grossman JE, Demling RH, Duy ND, Mosher DF. Response of plasma fibronectin to major body burn. J Trauma. 1980 Nov;20(11):967-70.
11.Boughton BJ, Simpson A. Plasma fibronectin in acute leukaemia. Br J Haematol. 1982 Jul;51(3):487-91.
12.陈元仲,吕联煌等.血液疾病血浆纤维结合蛋白水平的研究.中国实验临床免疫学杂志,1991,3:30-32.
13.Kwon AH, Qiu Z, Nagahama H, Kaibori M, et al. Fibronectin suppresses apoptosis and protects mice from endotoxic shock. Transplant Proc. 2004 Oct;36(8):2432-5.
14.Jarstrand C,et al.Fibronectin increases the motility phogacytosis and NBT (nitroblue tetrazolium) reduction of granulocytes.J.clin Lab Immunol.1982,8:59
15.Mar E.Opsonic fibronectin deficiency and sepsis.Ann surg.1982,195:340
16.Deno DC, McCafferty MH, Saba TM, et al. Mechanism of acute depletion of plasma fibronectin following thermal injury in rats. Appearance of a gelatinlike ligand in plasma. J Clin Invest. 1984 Jan;73(1):20-34.
17.La Celle P, Blumenstock FA, McKinley C, et al. Blood-borne collagenous debris complexes with plasma fibronectin after thermal injury. Blood. 1990 Jan 15;75(2):470-8.
18.Saba TM. Physiology and physiopathology of the reticuloendothelial system. Arch Intern Med. 1970 Dec;126(6):1031-52.
19.van Deuren M, Dofferhoff AS, van der Meer JW. Cytokines and the response to infection. J Pathol. 1992 Dec;168(4):349-56.
20.Josephs MD, Bahjat FR, Fukuzuka K,et al. Lipopolysaccharide and D-galactosamine-induced hepatic injury is mediated by TNF-alpha and not by Fas ligand. Am J Physiol Regul Integr Comp Physiol. 2000 May;278(5):R1196-201.
21.Rotundo RF, Curtis TM, Shah MD, et al. TNF-alpha disruption of lung endothelial integrity: reduced integrin mediated adhesion to fibronectin. Am J Physiol Lung Cell Mol Physiol. 2002 Feb;282
22.Saba TM, Niehaus GD, Scovill WA, et al. Lung vascular permeability after reversal of fibronectin deficiency in septic sheep. Correlation with patient studies. Ann Surg. 1983 Nov;198(5):654-62.
23.金惠铭,陈达信. 内毒素休克时血浆 FN 与微血管通透性的关系.上海医科大学学报.1990,17,6:401-404.
24.Brien TP, Reddy PP, Vincent PA, et al. Lung matrix deposition of normal and alkylated plasma fibronectin: response to postsurgical sepsis. Am J Physiol. 1998 Mar;274(3 Pt 1):L432-43.
25.Deno DC, Saba TM, Lewis EP. Kinetics of endogenously labeled plasma fibronectin: incorporation into tissues. Am J Physiol. 1983 Oct;245(4):R564-75.
26.Charash WE, Vincent PA, Saba TM, et al. Immunofluorescent analysis of plasma fibronectin incorporation into the lung during acute inflammatory vascular injury. Am Rev Respir Dis. 1993 Aug;148(2):467-76.
27.Gauperaa T, Seljelid R. Plasma fibronectin is sequestered into tissue damaged by inflammation and trauma. Acta Chir Scand. 1986 Feb;152:85-90.
28.Charash WE, Vincent PA, McKeown-Longo PJ, et al. Kinetics of plasma fibronectin: increased lung tissue incorporation after postoperative bacteremia. Am J Physiol. 1991 Mar;260(3 Pt 2):R553-62.
29.Jin HM, Vincent PA, Charash WE, et al. Incorporation of circulating fibronectin into various tissues during sepsis: colocalization with endogenous tissue fibronectin. Exp Mol Pathol. 1991 Dec;55(3):203-16.
30.Rebres RA, McKeown-Longo PJ, Vincent PA, et al Extracellular matrix incorporation of normal and NEM-alkylated fibronectin: liver and spleen deposition. Am J Physiol. 1995 Dec;269(6 Pt 1):G902-12.
31.Ni H, Yuen PS, Papalia JM, et al. Plasma fibronectin promotes thrombus growth and stability in injured arterioles. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2415-9.
32.Tsai WB, Horbett TA. The role of fibronectin in platelet adhesion to plasma preadsorbed polystyrene. J Biomater Sci Polym Ed. 1999;10(2):163-81.
33.Ni H, Denis CV, Subbarao S, et al. Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen. J Clin Invest. 2000 Aug;106(3):385-92.
34.Kwak D, Wu Y, Horbett TA. Fibrinogen and von Willebrand's factor adsorption are both required for platelet adhesion from sheared suspensions to polyethylene preadsorbed with blood plasma. J Biomed Mater Res A. 2005 Jul 1;74(1):69-83.
35.Qwarnstrom EE, Ostberg CO, Turk GL,et al. Fibronectin attachment activates the NF-kappa B p50/p65 heterodimer in fibroblasts and smooth muscle cells. J Biol Chem. 1994 Dec 9;269(49):30765-8.
36.Jacobson MD, Burne JF, King MP,et al. Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature. 1993 Jan 28;361(6410):365-9.
37.Blumenstock FA, Valeri CR, Saba TM,et al. Progressive loss of fibronectin-mediated opsonic activity in plasma cryoprecipitate with storage. Role of fibronectin fragmentation. Vox Sang. 1988;54(3):129-37.
38.Andersson E ,Rydengard V, Sonesson A et al. Antimicrobial activities of heparin-binding peptides. Eur J Biochem.2004 Mar; 271(6):1219-26.
39.Stack MS, Pizzo SV. Modulation of tissue plasminogen activator-catalyzed plasminogen activation by synthetic peptides derived from the amino-terminal heparin binding domain of fibronectin. J Biol Chem. 1993 Sep 5; 268(25): 18924-8.
40.Jalkanen S, Jalkanen M. Lymphocyte CD44 binds the COOH-terminal heparin-binding domain of fibronectin. J Cell Biol. 1992 Feb; 116(3):817-25.
41.Yasuda T, Kakinuma T, Julovi Sm, et al. COOH-terminal heparin-binding fibronectin fragment induces nitric oxide production in rheumatoid cartilage through CD44. Rheumatology(Oxford). 2004Sep;43(9):1116-20.
42.McCarthy JB, Skubitz AP, Palm SL, et al. Metastasis inhibition of different tumor types by purified laminin fragment and a heparin-binding fragment of fibronectin. J Natl Cancer Inst.1988Mar 16;80(2):108-16.
43.Woods A, McCarthy JB, Furcht LT, Couchman JB. A synthetic peptide from COOH-terminal heparin-binding domain of fibronectin promotes focal adhesion formation. Mol Biol Cell. 1993 Jun; 4(6);605-13.
44.Verfaillie CM, Benis A, Iida J, et al. Adhesion of committed human hematopoietic progenitors to synthetic peptides from the C-terminal heparin-binding domain of fibronectin: cooperation between the integrin alpha 4 beta and the CD44 adhesion receptor. Blood 1994 Sep 15; 84(6):1802-11.
1.Mosesson MW, Amrani DL. The structure and biologic activities of plasma fibronectin. Blood. 1980 Aug;56(2):145-58.
2.Pankov R, Yamada KM. Fibronectin at a glance. J Cell Sci. 2002 Oct 15;115(Pt 20):3861-3.
3.Debra J,Romberger.Fibronectin[J].Biochem.cell biol.(1997)29,939-943.
4.Gomez-Bravo Topete E, Castillo-Lechuga C, et al. Predictive value of fetal fibronectin for preterm labor. Cir Cir. 2004 Nov-Dec;72(6):491-4.
5.Takagi J. Structural basis for ligand recognition by RGD (Arg-Gly-Asp)-dependent integrins. Biochem Soc Trans. 2004 Jun;32(Pt3):403-6.
6.Liao YF, Gotwals PJ, Koteliansky VE, et al. The EIIIA segment of fibronectin is a ligand for integrins alpha 9beta 1 and alpha 4beta 1 providing a novel mechanism for regulating cell adhesion by alternative splicing. J Biol Chem. 2002 Apr 26;277(17):14467-74.
7.Plow,E.F.,Haas,T.A.,Zhang,L,et al. Ligand binding to intergrins. J.Biol.Chem.275,21785-21788.
8.Mostafavi-Pour,Askari JA,Whittard JD,et al.Identification of a novel heparin-binding site in the alternatively spliced IIICS region of fibronectin: roles of integrins and proteoglycans in cell adhesion to fibronectin splice variants.Matrix Biol.20,63-73.
9.Leikina,E,Mertts,M.V.,Kuznetsova,et al. Type I collagen is thermally unstable at body temperature. Proc.Natl.Acad.Sci.USA 99,1314-1318.
10. CorbettSA,SchwarzbauerJE.Requirements for α5β1 intergrin-mediated retraction of fibronectin-fibrin matrices.J Biol Chem,1999,274:20943-48.
11.Jin HM, Vincent PA, Charash WE, et al. Incorporation of circulating fibronectin into various tissues during sepsis: colocalization withendogenous tissue fibronectin. Exp Mol Pathol. 1991 Dec;55(3):203-16.
12.Wierzbicka-Patynowski I, Schwarzbauer JE. The ins and outs of fibronectin matrix assembly.J Cell Sci. 2003 Aug 15;116(Pt 16):3269-76..
13.Mao Y, Schwarzbauer JE. Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol. 2005 Sep;24(6):389-99.
14.Hume DA. The mononuclear phagocyte system.Curr Opin Immunol. 2006 Feb;18(1):49-53.
15.Patel VP,Lodish HF.A fibronectin matrixs is requires for differentiation of murine and its erythroleukemia cell into reticulocytes.J Cell Biol.1987,105:3105-3118.
16.Lanser ME, Saba TM. Opsonic fibronectin is necessary for optimal serum-mediated phagocytosis of Staphylococcus aureus by human neutrophils. Adv Shock Res. 1982;8:111-7.
17.Damiano J S , Cress A E , Hazlehurst L A , et al. Cell adhesion mediated drug resistance (CAM2DR) : role of integrins and resistance to apoptosis in human myeloma cell lines.Blood ,1999 ,93 :1658 - 1667.
18.Sethi T, Rintoul R C , Moore SM, et al. Extracellular matrix proteins protect small cell lung cancer cells against apoptosis : A mechanism for small cell lung cancer growth and drug resistance in vivo. Nature Medicine ,1999 ,5 : 662 - 668.
19.Qwarnstrom EE, Ostberg CO, Turk GL,et al. Fibronectin attachment activates the NF-kappa B p50/p65 heterodimer in fibroblasts and smooth muscle cells. J Biol Chem. 1994 Dec 9;269(49):30765-8.
20.Mohri H, Katoh K, Iwamatsu A, et al. The novel recognition site in the C-terminal heparin-binding domain of fibronectin by integrin alpha 4 beta 1 receptor on HL-60 cells.Exp Cell Res. 1996 Feb 1;222(2):326-32.
21.Coll JM, Luborsky SW, Mora PT. Metabolically labeled cell membrane proteins in spontaneously and in SV40 virus transformed mousefibroblasts.Biochemistry. 1977 Jul 12;16(14):3169-77.
2. Ruiz G, Veiga J, Luisa Gomez-Lus,et al. Plasmatic concentrations of fibronectin as marker of clinical course among septic patients. Enferm Infecc Microbiol Clin. 2001 Mar;19(3):93-8.
3.Saba TM, F.A.Blumenstock, WA Scovill, et al. Cryoprecipitate reversal of opsonic α2-surface binding glycoprotein deficiency in septic surgical and trauma patients. Science 1978,201:622-624.
4.Saba TM, F.A.Blumenstock, DM Shah, et al. Reversal of fibronectin and opsonic deficiency in patients: a controlled study. Ann.surg 1984,199:87-96.
5.吴勇, 陈元仲,吕联煌等. 纤维连接蛋白对内毒素血症小鼠保护作用的实验研究.中国病理生理杂志,2003,(06):799-802.
6.Yong Wu, Yuan-zhong Chen, Hui-fang Huang,et al. Recombinant fibronectin polypeptide antagonizes hepaticfailure induced by endotoxin in mice, Acta Pharmacol Sin 2004 Jun; 25 (6): 783-788
7.Pankov R, Yamada KM. Fibronectin at a glance. J Cell Sci. 2002 Oct 15;115(Pt 20):3861-3.
8.Leist M,Gantner F,Bohlinger I,et al.Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models.Am J Pathol.1995,146(5):1220-1234
9.杨宇飞,周蔼祥等. 免疫性血小板减少性紫癜动物模型的建立. 中华血液学杂志.1994,15:160-161.
10.Grossman JE, Demling RH, Duy ND, Mosher DF. Response of plasma fibronectin to major body burn. J Trauma. 1980 Nov;20(11):967-70.
11.Boughton BJ, Simpson A. Plasma fibronectin in acute leukaemia. Br J Haematol. 1982 Jul;51(3):487-91.
12.陈元仲,吕联煌等.血液疾病血浆纤维结合蛋白水平的研究.中国实验临床免疫学杂志,1991,3:30-32.
13.Kwon AH, Qiu Z, Nagahama H, Kaibori M, et al. Fibronectin suppresses apoptosis and protects mice from endotoxic shock. Transplant Proc. 2004 Oct;36(8):2432-5.
14.Jarstrand C,et al.Fibronectin increases the motility phogacytosis and NBT (nitroblue tetrazolium) reduction of granulocytes.J.clin Lab Immunol.1982,8:59
15.Mar E.Opsonic fibronectin deficiency and sepsis.Ann surg.1982,195:340
16.Deno DC, McCafferty MH, Saba TM, et al. Mechanism of acute depletion of plasma fibronectin following thermal injury in rats. Appearance of a gelatinlike ligand in plasma. J Clin Invest. 1984 Jan;73(1):20-34.
17.La Celle P, Blumenstock FA, McKinley C, et al. Blood-borne collagenous debris complexes with plasma fibronectin after thermal injury. Blood. 1990 Jan 15;75(2):470-8.
18.Saba TM. Physiology and physiopathology of the reticuloendothelial system. Arch Intern Med. 1970 Dec;126(6):1031-52.
19.van Deuren M, Dofferhoff AS, van der Meer JW. Cytokines and the response to infection. J Pathol. 1992 Dec;168(4):349-56.
20.Josephs MD, Bahjat FR, Fukuzuka K,et al. Lipopolysaccharide and D-galactosamine-induced hepatic injury is mediated by TNF-alpha and not by Fas ligand. Am J Physiol Regul Integr Comp Physiol. 2000 May;278(5):R1196-201.
21.Rotundo RF, Curtis TM, Shah MD, et al. TNF-alpha disruption of lung endothelial integrity: reduced integrin mediated adhesion to fibronectin. Am J Physiol Lung Cell Mol Physiol. 2002 Feb;282
22.Saba TM, Niehaus GD, Scovill WA, et al. Lung vascular permeability after reversal of fibronectin deficiency in septic sheep. Correlation with patient studies. Ann Surg. 1983 Nov;198(5):654-62.
23.金惠铭,陈达信. 内毒素休克时血浆 FN 与微血管通透性的关系.上海医科大学学报.1990,17,6:401-404.
24.Brien TP, Reddy PP, Vincent PA, et al. Lung matrix deposition of normal and alkylated plasma fibronectin: response to postsurgical sepsis. Am J Physiol. 1998 Mar;274(3 Pt 1):L432-43.
25.Deno DC, Saba TM, Lewis EP. Kinetics of endogenously labeled plasma fibronectin: incorporation into tissues. Am J Physiol. 1983 Oct;245(4):R564-75.
26.Charash WE, Vincent PA, Saba TM, et al. Immunofluorescent analysis of plasma fibronectin incorporation into the lung during acute inflammatory vascular injury. Am Rev Respir Dis. 1993 Aug;148(2):467-76.
27.Gauperaa T, Seljelid R. Plasma fibronectin is sequestered into tissue damaged by inflammation and trauma. Acta Chir Scand. 1986 Feb;152:85-90.
28.Charash WE, Vincent PA, McKeown-Longo PJ, et al. Kinetics of plasma fibronectin: increased lung tissue incorporation after postoperative bacteremia. Am J Physiol. 1991 Mar;260(3 Pt 2):R553-62.
29.Jin HM, Vincent PA, Charash WE, et al. Incorporation of circulating fibronectin into various tissues during sepsis: colocalization with endogenous tissue fibronectin. Exp Mol Pathol. 1991 Dec;55(3):203-16.
30.Rebres RA, McKeown-Longo PJ, Vincent PA, et al Extracellular matrix incorporation of normal and NEM-alkylated fibronectin: liver and spleen deposition. Am J Physiol. 1995 Dec;269(6 Pt 1):G902-12.
31.Ni H, Yuen PS, Papalia JM, et al. Plasma fibronectin promotes thrombus growth and stability in injured arterioles. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2415-9.
32.Tsai WB, Horbett TA. The role of fibronectin in platelet adhesion to plasma preadsorbed polystyrene. J Biomater Sci Polym Ed. 1999;10(2):163-81.
33.Ni H, Denis CV, Subbarao S, et al. Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen. J Clin Invest. 2000 Aug;106(3):385-92.
34.Kwak D, Wu Y, Horbett TA. Fibrinogen and von Willebrand's factor adsorption are both required for platelet adhesion from sheared suspensions to polyethylene preadsorbed with blood plasma. J Biomed Mater Res A. 2005 Jul 1;74(1):69-83.
35.Qwarnstrom EE, Ostberg CO, Turk GL,et al. Fibronectin attachment activates the NF-kappa B p50/p65 heterodimer in fibroblasts and smooth muscle cells. J Biol Chem. 1994 Dec 9;269(49):30765-8.
36.Jacobson MD, Burne JF, King MP,et al. Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature. 1993 Jan 28;361(6410):365-9.
37.Blumenstock FA, Valeri CR, Saba TM,et al. Progressive loss of fibronectin-mediated opsonic activity in plasma cryoprecipitate with storage. Role of fibronectin fragmentation. Vox Sang. 1988;54(3):129-37.
38.Andersson E ,Rydengard V, Sonesson A et al. Antimicrobial activities of heparin-binding peptides. Eur J Biochem.2004 Mar; 271(6):1219-26.
39.Stack MS, Pizzo SV. Modulation of tissue plasminogen activator-catalyzed plasminogen activation by synthetic peptides derived from the amino-terminal heparin binding domain of fibronectin. J Biol Chem. 1993 Sep 5; 268(25): 18924-8.
40.Jalkanen S, Jalkanen M. Lymphocyte CD44 binds the COOH-terminal heparin-binding domain of fibronectin. J Cell Biol. 1992 Feb; 116(3):817-25.
41.Yasuda T, Kakinuma T, Julovi Sm, et al. COOH-terminal heparin-binding fibronectin fragment induces nitric oxide production in rheumatoid cartilage through CD44. Rheumatology(Oxford). 2004Sep;43(9):1116-20.
42.McCarthy JB, Skubitz AP, Palm SL, et al. Metastasis inhibition of different tumor types by purified laminin fragment and a heparin-binding fragment of fibronectin. J Natl Cancer Inst.1988Mar 16;80(2):108-16.
43.Woods A, McCarthy JB, Furcht LT, Couchman JB. A synthetic peptide from COOH-terminal heparin-binding domain of fibronectin promotes focal adhesion formation. Mol Biol Cell. 1993 Jun; 4(6);605-13.
44.Verfaillie CM, Benis A, Iida J, et al. Adhesion of committed human hematopoietic progenitors to synthetic peptides from the C-terminal heparin-binding domain of fibronectin: cooperation between the integrin alpha 4 beta and the CD44 adhesion receptor. Blood 1994 Sep 15; 84(6):1802-11.
1.Mosesson MW, Amrani DL. The structure and biologic activities of plasma fibronectin. Blood. 1980 Aug;56(2):145-58.
2.Pankov R, Yamada KM. Fibronectin at a glance. J Cell Sci. 2002 Oct 15;115(Pt 20):3861-3.
3.Debra J,Romberger.Fibronectin[J].Biochem.cell biol.(1997)29,939-943.
4.Gomez-Bravo Topete E, Castillo-Lechuga C, et al. Predictive value of fetal fibronectin for preterm labor. Cir Cir. 2004 Nov-Dec;72(6):491-4.
5.Takagi J. Structural basis for ligand recognition by RGD (Arg-Gly-Asp)-dependent integrins. Biochem Soc Trans. 2004 Jun;32(Pt3):403-6.
6.Liao YF, Gotwals PJ, Koteliansky VE, et al. The EIIIA segment of fibronectin is a ligand for integrins alpha 9beta 1 and alpha 4beta 1 providing a novel mechanism for regulating cell adhesion by alternative splicing. J Biol Chem. 2002 Apr 26;277(17):14467-74.
7.Plow,E.F.,Haas,T.A.,Zhang,L,et al. Ligand binding to intergrins. J.Biol.Chem.275,21785-21788.
8.Mostafavi-Pour,Askari JA,Whittard JD,et al.Identification of a novel heparin-binding site in the alternatively spliced IIICS region of fibronectin: roles of integrins and proteoglycans in cell adhesion to fibronectin splice variants.Matrix Biol.20,63-73.
9.Leikina,E,Mertts,M.V.,Kuznetsova,et al. Type I collagen is thermally unstable at body temperature. Proc.Natl.Acad.Sci.USA 99,1314-1318.
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