Research Topics
Genomes and Genes | Jay L DegenSummaryAffiliation: Children's Hospital Medical Center Country: USA Publications
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Publications
Fibrin and fibrinolysis in infection and host defenseJ L Degen
Division of Developmental Biology, Children s Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, OH, USA
J Thromb Haemost 5:24-31. 2007..Detailed studies of the inflammatory response in mice with genetically-imposed modifications in coagulation and fibrinolytic factors underscore the regulatory crosstalk between the hemostatic and immune systems...
Plasmin-mediated proteolysis is required for hepatocyte growth factor activation during liver repairKumar Shanmukhappa
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
J Biol Chem 284:12917-23. 2009..These findings support a fibrinolysis-unrelated role for Plg in modulating cell proliferation and migration by activation of Hgf...- Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motifMatthew J Flick
Cincinnati Children s Hospital Research Foundation and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 3039, USA
J Clin Invest 117:3224-35. 2007..Thus, fibrin(ogen) is an important, but context-dependent, determinant of arthritis, and one mechanism linking fibrin(ogen) to joint disease is coupled to alphaMbeta2-mediated inflammatory processes... - Plasminogen deficiency results in poor clearance of non-fibrin matrix and persistent activation of hepatic stellate cells after an acute injuryV L Ng
Divisions of Gastroenterology, Hepatology, and Nutrition, Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229-3039, USA
J Hepatol 35:781-9. 2001..CONCLUSIONS: Proteolytic clearance of non-fibrin matrix components by plasminogen must occur for HSCs to restore the quiescent phenotype during liver repair... - Plasminogen deficiency leads to impaired lobular reorganization and matrix accumulation after chronic liver injuryJ F Pohl
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children s Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA
Am J Pathol 159:2179-86. 2001..Taken together, these data suggest that the progressive accumulation of fibrin-unrelated matrix substrates in Plg(0) livers after a chronic injury results from the combined effects of impaired proteolysis and increased matrix production... - Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiencyT H Bugge
Division of Developmental Biology, Children s Hospital Research Foundation, Cincinnati, Ohio 45229, USA
Cell 87:709-19. 1996..Mice deficient in Plg and Fib are phenotypically indistinguishable from Fib-deficient mice. These data suggest that the fundamental and possibly only essential physiological role of Plg is fibrinolysis... - Fibrinogen deficiency is compatible with the development of atherosclerosis in miceQ Xiao
Division of Developmental Biology, Children s Hospital Research Foundation, Cincinnati, Ohio 45229, USA
J Clin Invest 101:1184-94. 1998.... - The development of inflammatory joint disease is attenuated in mice expressing the anticoagulant prothrombin mutant W215A/E217AMatthew J Flick
Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, OH, USA
Blood 117:6326-37. 2011..These studies provide a proof-of-principle that pro/thrombin variants engineered with altered substrate specificity may offer therapeutic opportunities for limiting inflammatory disease processes... - Mechanisms linking hemostatic factors to tumor growth in miceJay L Degen
Division of Developmental Biology, Children's Hospital Research Foundation and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
Pathophysiol Haemost Thromb 33:31-5. 2003 - Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient miceT T Suh
Division of Basic Science Research, Children s Hospital Research Foundation, Cincinnati, Ohio 45229, USA
Genes Dev 9:2020-33. 1995..Microscopic analysis of spontaneous lesions found in A alpha-/- mice suggests that fibrin(ogen) plays a fundamental role in the organization of cells at sites of injury... - Biological effects of targeted inactivation of hepatocyte growth factor-like protein in miceJ A Bezerra
Division of Gastroenterology and Nutrition, Children s Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229 3039, USA
J Clin Invest 101:1175-83. 1998..HGFL-deficient mice will provide a valuable means to assess the role of HGFL in hepatic and systemic responses to inflammatory and infectious stimuli in vivo... - Genetic manipulation of fibrinogen and fibrinolysis in miceJ L Degen
Children s Hospital Research Foundation, Children s Hospital Medical Center, IDR NRB Room 2042, 3333 Burnet Avenue, Cincinnati, Ohio 45229 3039, USA
Ann N Y Acad Sci 936:276-90. 2001..Studies illustrating the role and interplay of these factors in disease progression are highlighted... - Plasminogen activators direct reorganization of the liver lobule after acute injuryJ A Bezerra
Division of Gastroenterology and Nutrition, Children s Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229 3039, USA
Am J Pathol 158:921-9. 2001..These data demonstrate that tPA and uPA play a critical role in hepatic repair via proteolysis of matrix elements and clearance of cellular debris from the field of injury... - Persistent corneal haze after excimer laser photokeratectomy in plasminogen-deficient miceA F Drew
Children s Hospital Research Foundation, Cincinnati, Ohio, USA
Invest Ophthalmol Vis Sci 41:67-72. 2000..Fibrin deposition and resolution after excimer laser photokeratectomy were investigated in relation to corneal repair and restoration of clarity in mice with a genetic deficiency of plasminogen... - Genetic interactions between the coagulation and fibrinolytic systemsJ L Degen
Children s Hospital Research Foundation, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
Thromb Haemost 86:130-7. 2001..New insights regarding the role(s) and interplay of hemostatic factors that have emerged from detailed studies of mice carrying multiple deficits in coagulation and fibrinolytic system components are highlighted... - Plasminogen deficiency leads to impaired remodeling after a toxic injury to the liverJ A Bezerra
Children s Hospital Research Foundation, Department of Pediatrics, University of Cincinnati, OH 45229 3039, USA
Proc Natl Acad Sci U S A 96:15143-8. 1999.... - Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domainNetanel A Horowitz
Cancer and Blood Diseases Institute, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
Blood 118:2889-95. 2011.... - Deleterious effects of plasminogen activators in neonatal cerebral hypoxia-ischemiaFaisal Adhami
Division of Developmental Biology and Division of Neurology, Cincinnati Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
Am J Pathol 172:1704-16. 2008.... - Plasminogen deficiency causes severe thrombosis but is compatible with development and reproductionT H Bugge
Division of Basic Science Research, Children s Hospital Research Foundation, Cincinnati, Ohio 45229, USA
Genes Dev 9:794-807. 1995..Therefore, Plg plays a pivotal role in fibrinolysis and hemostasis but is not essential for urokinase proenzyme activation, development, or growth to sexual maturity... - Urokinase-type plasminogen activator is effective in fibrin clearance in the absence of its receptor or tissue-type plasminogen activatorT H Bugge
Division of Developmental Biology, Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
Proc Natl Acad Sci U S A 93:5899-904. 1996.... 
Hemostatic factors, innate immunity and malignancyJay L Degen
Cancer and Blood Diseases Institute, Cincinnati Children s Research Foundation, Cincinnati, OH 45229, USA
Thromb Res 129:S1-5. 2012....- Fibrinogen deficiency, but not plasminogen deficiency, increases mortality synergistically in combination with sickle hemoglobin SAD in transgenic miceNancy J Roszell
Comprehensive Sickle Cell Center, Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
Am J Hematol 82:1044-8. 2007..Rather, our findings suggest that the contribution of fibrinogen to tissue repair may in some contexts limit sickle cell disease pathophysiology... - Role of fibrinogen- and platelet-mediated hemostasis in mouse embryogenesis and reproductionJ S Palumbo
Cincinnati Children s Hospital Research Foundation, Cincinnati, Ohio, USA
J Thromb Haemost 2:1368-79. 2004..These findings support the notion that the function of coagulation factors for in utero development and pregnancy is mechanistically distinct from their ability to mediate the formation of hemostatic platelet-fibrin(ogen) aggregates... - Wound-healing defects in mice lacking fibrinogenA F Drew
Division of Developmental Biology, Children s Hospital Research Foundation, 3333 Burnet Ave, Cincinnati, PH 45229 3039, USA
Blood 97:3691-8. 2001..However, fibrin (ogen) is important for appropriate cellular migration and organization within wound fields and in initially establishing wound strength and stability. (Blood. 2001;97:3691-3698).. - Prothrombin deficiency results in embryonic and neonatal lethality in miceW Y Sun
Division of Developmental Biology, Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
Proc Natl Acad Sci U S A 95:7597-602. 1998..This study directly demonstrates that FII is important in maintaining vascular integrity during development as well as postnatal life... - Impaired platelet aggregation and sustained bleeding in mice lacking the fibrinogen motif bound by integrin alpha IIb beta 3K Holmbäck
Division of Developmental Biology, Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
EMBO J 15:5760-71. 1996..Despite the preservation of clotting function, gamma delta 5/gamma delta 5 mice were unable to control blood loss following a surgical challenge and occasionally developed fatal neonatal bleeding events... - Plasminogen is a critical determinant of vascular remodeling in miceA F Drew
Children s Hospital Research Foundation, Cincinnati, OH 45229 3039, USA
Circ Res 87:133-9. 2000..In addition, these studies reveal a fibrin-independent role of plasminogen in preventing medial atrophy in challenged vessels... - Urokinase-type plasminogen activator supports liver repair independent of its cellular receptorKumar Shanmukhappa
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children s Hospital Medical Center and the Department of Pediatrics of the University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
BMC Gastroenterol 6:40. 2006..Based on the efficient activation of plasminogen when uPA is bound to its receptor (uPAR) and on the role of uPA in plasmin-mediated liver repair, we hypothesized that uPA requires uPAR for efficient liver repair... - Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanismsJoseph S Palumbo
Divisions of Hematology, Children s Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
Blood 110:133-41. 2007..However, TF also supported the early success of micrometastases through an additional mechanism independent of natural killer cells, but coupled to circulating prothrombin... - Plasminogen directs the pleiotropic effects of uPA in liver injury and repairAngela R Currier
Division of Gastroenterology, Hepatology, and Nutrition, Children s Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
Am J Physiol Gastrointest Liver Physiol 284:G508-15. 2003..These data demonstrate that plasminogen directs the hepatocyte injury induced by uPAT and mediates the reparative properties of uPA in the liver... - Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cellsJoseph S Palumbo
Division of Hematology Oncology, Children s Hospital Research Foundation, and University of Cincinnati College of Medicine, Cincinnati, OH, USA
Blood 105:178-85. 2005.... - Crescentic glomerulonephritis is diminished in fibrinogen-deficient miceA F Drew
Division of Developmental Biology, Children s Hospital Research Foundation, Cincinnati, Ohio 45229 3039, USA
Am J Physiol Renal Physiol 281:F1157-63. 2001.... - Reduced metastasis of Polyoma virus middle T antigen-induced mammary cancer in plasminogen-deficient miceT H Bugge
Division of Developmental Biology, Children s Hospital Research Foundation, Cincinnati, Ohio 45229, USA
Oncogene 16:3097-104. 1998..The data provide direct evidence that plasmin(ogen) is a tumor progression factor in PymT-induced mammary cancer, and support the hypothesis that hemostatic factors play an important role in tumor biology... - The receptor for urokinase-type plasminogen activator is not essential for mouse development or fertilityT H Bugge
Division of Basic Science, Children s Hospital Research Foundation, Cincinnati, Ohio 45229, USA
J Biol Chem 270:16886-94. 1995..These mice provide a means to test the proposed function of uPA/uPAR in wound repair, atherogenesis, and tumor cell invasion in vivo... - Ligneous conjunctivitis in plasminogen-deficient miceA F Drew
Divisions of Developmental Biology and Pathology, Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
Blood 91:1616-24. 1998.... - Factor XIII transglutaminase supports hematogenous tumor cell metastasis through a mechanism dependent on natural killer cell functionJ S Palumbo
Division of Hematology Oncology, Cincinnati Children s Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
J Thromb Haemost 6:812-9. 2008..As the transglutaminase that ultimately stabilizes platelet/fibrin thrombi through the covalent crosslinking of fibrin, factor (F) XIII is another thrombin substrate that is likely to support hematogenous metastasis... - The Ron/STK receptor tyrosine kinase is essential for peri-implantation development in the mouseR S Muraoka
Graduate Program in Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 3039, USA
J Clin Invest 103:1277-85. 1999..These results demonstrate a novel role for Ron in early mouse development and suggest that Ron plays a limiting role in the inflammatory response... - Hepatic to pancreatic switch defines a role for hemostatic factors in cellular plasticity in miceKumar Shanmukhappa
Division of Pediatric Gastroenterology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
Proc Natl Acad Sci U S A 102:10182-7. 2005..Collectively, these data reveal a regulatory role for the hemostatic factors plasmin(ogen) and fibrin(ogen) in cellular plasticity within adult tissues of the digestive system... - Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient miceJoseph S Palumbo
Division of Hematology Oncology, Children s Hospital Research Foundation and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 3039, USA
Cancer Res 62:6966-72. 2002..These studies suggest that therapeutic strategies focusing on hemostatic factors may be effective in controlling solid tumor metastasis, particularly if used for the treatment of micrometastatic disease... - Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulationT H Bugge
Division of Developmental Biology, Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
Proc Natl Acad Sci U S A 93:6258-63. 1996..These studies indicate that TF plays an indispensable role in establishing and/or maintaining vascular integrity in the developing embryo at a time when embryonic and extraembryonic vasculatures are fusing and blood circulation begins... - Plasminogen deficiency accelerates vessel wall disease in mice predisposed to atherosclerosisQ Xiao
Division of Developmental Biology, Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
Proc Natl Acad Sci U S A 94:10335-40. 1997..These studies provide direct evidence that circulating hemostatic factors strongly influence vessel wall disease in the context of a disorder in lipid metabolism... - Growth and dissemination of Lewis lung carcinoma in plasminogen-deficient miceT H Bugge
Divisions of Developmental Biology and Pathology, Children s Hospital Research Foundation, Cincinnati, OH, USA
Blood 90:4522-31. 1997.... - Plasminogen supports tumor growth through a fibrinogen-dependent mechanism linked to vascular patencyJoseph S Palumbo
Division of Hematology/Oncology, Children's Hospital Research Foundation, and University of Cincinnati College of Medicine, OH 45229, USA
Blood 102:2819-27. 2003..Furthermore, these studies suggest that one target of plasmin(ogen) relevant to tumor progression in vivo is intravascular fibrin... - Fibrin but not adsorbed fibrinogen supports fibronectin assembly by spread platelets. Effects of the interaction of alphaIIb beta3 with the C terminus of the fibrinogen gamma-chainJaehyung Cho
Molecular and Cellular Pharmacology Program and Department of Medicine, University of Wisconsin Madison School of Medicine, Madison, Wisconsin 53706, USA
J Biol Chem 280:35490-8. 2005..This interaction is less dominant when platelets adhere to fibrin, resulting in enhanced fibronectin assembly... - The thrombomodulin-protein C system is essential for the maintenance of pregnancyBerend Isermann
Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin, USA
Nat Med 9:331-7. 2003..These findings show a new function for the thrombomodulin-protein C system in controlling the growth and survival of trophoblast cells in the placenta. This function is essential for the maintenance of pregnancy... - Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in plateletsDubravka Kufrin
Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, ARC; Rm 317, Philadelphia, PA 19104, USA
Blood 102:926-33. 2003..These studies show the feasibility of delivering fibrinolytic agents to sites of incipient thrombus formation through selective storage in platelets and offer a new strategy to prevent thrombosis and hemorrhage... - Localization of regulatory elements mediating constitutive and cytokine-stimulated plasminogen gene expressionFelizabel Garcia Bannach
Department of Cell Biology, Division of Vascular Biology, Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 277:38579-88. 2002..These results indicate the presence of regulatory elements in the 5'-flanking region of the murine plasminogen promoter that may regulate murine plasminogen gene expression and, hence, plasmin activity... - Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivoMatthew J Flick
Children s Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 3039, USA
J Clin Invest 113:1596-606. 2004.... - The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune diseaseRyan A Adams
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA
J Exp Med 204:571-82. 2007.... - Plasmin deficiency does not alter endogenous murine amyloid beta levels in miceH Michael Tucker
Department of Physiology, Sanders Brown Center on Aging, University of Kentucky, 800 S Limestone St, Lexington, KY 40536 0230, USA
Neurosci Lett 368:285-9. 2004..Hence, although plasmin is potentially important in the degradation of A beta aggregates, we interpret these data as suggesting that plasmin does not regulate steady-state A beta levels in non-pathologic conditions... - Cerebral ischemia-hypoxia induces intravascular coagulation and autophagyFaisal Adhami
Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Room 3464, 3333 Burnet Ave, Cincinnati, OH 45229, USA
Am J Pathol 169:566-83. 2006..Together, these results suggest that ischemia-hypoxia is a powerful stimulus for spontaneous coagulation leading to reperfusion deficits and autophagic/lysosomal cell death in brain...