Title:
ANTI-FIBROSIS PHARMACEUTICAL COMPOSITION AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2022/127654
Kind Code:
A1
Abstract:
An anti-fibrosis pharmaceutical composition and an application thereof. The anti-fibrosis pharmaceutical composition specifically comprises: (a) an NRP1 inhibitor and/or a HIF2α inhibitor; and (b) an EPCR pathway activator that promotes the activity of an EPCR pathway. The anti-fibrosis pharmaceutical composition helps reduce organ fibrosis to a certain extent and promotes corresponding organ repair and regeneration.
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Inventors:
DING BISEN (CN)
CAO ZHONGWEI (CN)
CAO ZHONGWEI (CN)
Application Number:
PCT/CN2021/136240
Publication Date:
June 23, 2022
Filing Date:
December 08, 2021
Export Citation:
Assignee:
WEST CHINA SECOND UNIV HOSPITAL (CN)
International Classes:
A61P1/16; A61K38/00; A61P9/00; A61P11/00; A61P13/12; C07D277/56; C07D495/04
Domestic Patent References:
| WO2008040979A1 | 2008-04-10 | |||
| WO2015095048A1 | 2015-06-25 |
Other References:
CHEN YUTIAN; PU QIANG; MA YONGYUAN; ZHANG HUA; YE TINGHONG; ZHAO CHENGJIAN; HUANG XIAOJUAN; REN YAFENG; QIAO LINA; LIU HAN-MIN; ES: "Aging Reprograms the Hematopoietic-Vascular Niche to Impede Regeneration and Promote Fibrosis", CELL METABOLISM, CELL PRESS, vol. 33, no. 2, 22 December 2020 (2020-12-22), United States , pages 395, XP086481659, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2020.11.019
ELPEK GÜLSÜM ÖZLEM: "Neuropilins and liver", WORLD JOURNAL OF GASTROENTEROLOGY, vol. 21, no. 23, 21 June 2015 (2015-06-21), CN , pages 7065 - 7073, XP055944543, ISSN: 1007-9327, DOI: 10.3748/wjg.v21.i23.7065
CAO SHENG, YAQOOB USMAN, DAS AMITAVA, SHERGILL UDAY, JAGAVELU KUMARAVELU, HUEBERT ROBERT C., ROUTRAY CHITTARANJAN, ABDELMONEIM SOH: "Neuropilin-1 promotes cirrhosis of the rodent and human liver by enhancing PDGF/TGF-β signaling in hepatic stellate cells", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 120, no. 7, 1 July 2010 (2010-07-01), GB , pages 2379 - 2394, XP055944547, ISSN: 0021-9738, DOI: 10.1172/JCI41203
WU MING-HENG, CHEN YUH-LING, LEE KUEN-HAUR, CHANG CHE-CHANG, CHENG TSAI-MU, WU SZU-YUAN, TU CHAO-CHIANG, TSUI WAN-LIN: "Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-β- and PDGF-like signals in hepatic stellate cells", SCIENTIFIC REPORTS, vol. 7, no. 1, 1 December 2017 (2017-12-01), pages 1 - 16, XP055944554, DOI: 10.1038/s41598-017-11212-1
MATILLA LARA, ARRIETA VANESSA, JOVER EVA, GARCIA-PEÑA AMAIA, MARTINEZ-MARTINEZ ERNESTO, SADABA RAFAEL, ALVAREZ VIRGINIA, NAVARRO A: "Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1", CELLS, vol. 9, no. 7, pages 1 - 15, XP055944563, DOI: 10.3390/cells9071667
COPPLE BRYAN L., BUSTAMANTE JUAN J., WELCH TIMOTHY P., KIM NAM DEUK, MOON JEON-OK: "Hypoxia-inducible factor-dependent production of profibrotic mediators by hypoxic hepatocytes", LIVER INTERNATIONAL, vol. 29, no. 7, 1 August 2009 (2009-08-01), GB , pages 1010 - 1021, XP055944572, ISSN: 1478-3223, DOI: 10.1111/j.1478-3231.2009.02015.x
SCHIETKE RUTH E., HACKENBECK THOMAS, TRAN MAXINE, GÜNTHER REGINA, KLANKE BERND, WARNECKE CHRISTINA L., KNAUP KARL X., SHUKLA DEEPA: "Renal Tubular HIF-2α Expression Requires VHL Inactivation and Causes Fibrosis and Cysts", PLOS ONE, vol. 7, no. 1, January 2012 (2012-01-01), pages 1 - 12, XP055944576, DOI: 10.1371/journal.pone.0031034
SOPEL MRYANDA J., ROSIN NICOLE L., FALKENHAM ALEC G., BEZUHLY MICHAEL, ESMON CHARLES T., LEE TIMOTHY D. G., LIWSKI ROBERT S., LÉGA: "Treatment with Activated Protein C (aPC) Is Protective during the Development of Myocardial Fibrosis: An Angiotensin II Infusion Model in Mice", PLOS ONE, vol. 7, no. 9, 19 September 2012 (2012-09-19), pages 1 - 10, XP055944577, DOI: 10.1371/journal.pone.0045663
SUZUKI KOJI ET AL: "Protective role of activated protein C in lung and airway remodeling.", CRITICAL CARE MEDICINE, vol. 32, no. 5 Suppl, 1 May 2004 (2004-05-01), US , pages S262 - S265, XP009081045, ISSN: 0090-3493, DOI: 10.1097/01.CCM.0000129668.96935.A8
"Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology", SCIENCE, vol. 357, 2017
"Methylation determines fibroblast activation and fibrogenesis in the kidney", NATURE MEDICINE, vol. 16, 2010, pages 544 - 550
"A vascular niche and a VEGF-Nrpl loop regulate the initiation and sternness of skin tumours", NATURE, vol. 478, 2011, pages 399 - 403
"Platelets: covert regulators of lymphatic development", ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, vol. 30, 2010, pages 2368 - 2371
"Vascular endothelial growth factor-B acts as a coronary growth factor in transgenic rats without inducing angiogenesis, vascular leak, or inflammation", CIRCULATION, vol. 122, 2010, pages 1725 - 1733
"Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity.", CELL METAB, vol. 18, 2013, pages 478 - 489
"Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.", NATURE MEDICINE, vol. 22, 2016, pages 154 - 162
" Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis", SCIENCE TRANSLATIONAL MEDICINE, vol. 9, 2017
"Molecular mechanisms and clinical applications of angiogenesis", NATURE, vol. 473, 2011, pages 298 - 307
"Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity", CANCER CELL, vol. 24, 2013, pages 695 - 709
"Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective", NAT MED, vol. 9, 2003, pages 338 - 342
"Targeting HIF2 in Clear Cell Renal Cell Carcinoma", COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, vol. 81, 2016, pages 113 - 121
"Role of endothelial cell metabolism in vessel sprouting", CELL METAB, vol. 18, 2013, pages 634 - 647
"Macrophage regulation of tumor responses to anticancer therapies", CANCER CELL, vol. 23, 2013, pages 277 - 286
"Alveolar progenitor and stem cells in lung development, renewal and cancer", NATURE, 2014
"Translational strategies and challenges in regenerative medicine", NATURE MEDICINE, vol. 20, 2014, pages 814 - 821
"Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis", NATURE, vol. 505, 2014, pages 97 - 102
"Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration", NATURE, vol. 468, 2010, pages 310 - 315
"Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization", CELL, vol. 147, 2011, pages 539 - 553
"Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1", SCIENCE, vol. 324, 2009, pages 1289 - 1293
"Distinct mechanisms regulate TIMP-1 expression at different stages of phorbol ester-mediated differentiation of U937 cells", BIOCHEMISTRY, vol. 36, 1997, pages 2492 - 2500
"Molecular circuits in thrombosis and inflammation", THROMB HAEMOST, vol. 109, 2013, pages 416 - 420
"Therapy for fibrotic diseases: nearing the starting line", SCIENCE TRANSLATIONAL MEDICINE, vol. 5, no. 167, 2013, pages srl6l
"Infusion of mature megakaryocytes into mice yields functional platelets", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 120, 2010, pages 3917 - 3922
"Migrating Platelets Are Mechano-scavengers that Collect and Bundle Bacteria", CELL, vol. 171, 2017, pages 1368 - 1382
"Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung", CELL, vol. 176, 2019, pages 113 - 126
"Macrophage heterogeneity in tissues: phenotypic diversity and functions", IMMUNOL REV, vol. 262, 2014, pages 36 - 55
"Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins", SCIENCE, vol. 307, 2005, pages 265 - 268
"PARI signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells", NAT MED, vol. 21, 2015, pages 1307 - 1317
"Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance", SCIENCE TRANSLATIONAL MEDICINE, vol. 6, 2014, pages 231ra247
"Targeting of alphav integrin identifies a core molecular pathway that regulates fibrosis in several organs", NATURE MEDICINE, vol. 19, 2013, pages 1617 - 1624
"Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury", NATURE MEDICINE, vol. 15, 2009, pages 384 - 391
"Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function", CELL STEM CELL, vol. 15, 2014, pages 123 - 138
"Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis", NAT MED, vol. 13, 2007, pages 1349 - 1358
"Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes", NATURE MEDICINE, vol. 12, 2006, pages 557 - 567
"Targeting CXCR4-dependent immunosuppressive Ly6Clow monocytes improves antiangiogenic therapy in colorectal cancer", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 114, 2017, pages 10455 - 10460
"Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors", SCIENCE, vol. 344, 2014, pages 630 - 634
"HIF 1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression", NAT REV CANCER, vol. 12, 2011, pages 9 - 22
"Lung regeneration: mechanisms, applications and emerging stem cell populations", NATURE MEDICINE, vol. 20, 2014, pages 822 - 832
"Perivascular Glil+ progenitors are key contributors to injury-induced organ fibrosis", CELL STEM CELL, vol. 16, 2015, pages 51 - 66
"Age-dependent modulation of vascular niches for haematopoietic stem cells", NATURE, vol. 532, 2015, pages 380 - 384
"Aggravation of viral hepatitis by platelet-derived serotonin", NATURE MEDICINE, vol. 14, 2008, pages 756 - 761
"Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy", CELL STEM CELL, vol. 21, 2017, pages 120 - 134
"The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors", NATURE, vol. 544, 2017, pages 105 - 109
"Platelet-derived serotonin mediates liver regeneration", SCIENCE, vol. 312, 2006, pages 104 - 107
"Overexpressing endothelial cell protein C receptor alters the hemostatic balance and protects mice from endotoxin", J THROMB HAEMOST, vol. 3, 2005, pages 1351 - 1359
"WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature", NATURE, vol. 437, 2005, pages 417 - 421
"Platelet-macrophage partnership in innate immunity and inflammation", NATURE IMMUNOLOGY, vol. 14, 2013, pages 768 - 770
"Peptidylarginine deiminase 4 promotes age-related organ fibrosis", THE JOURNAL OF EXPERIMENTAL MEDICINE, vol. 214, 2017, pages 439 - 458
"Pulmonary fibrosis: patterns and perpetrators", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 122, 2012, pages 2756 - 2762
"Platelet-derived SDF-1 primes the pulmonary capillary vascular niche to drive lung alveolar regeneration", NATURE CELL BIOLOGY, vol. 17, 2015, pages 123 - 136
"Functional significance of the platelet immune receptors GPVI and CLEC-2", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 129, 2019, pages 12 - 23
"Endothelium-microenvironment interactions in the developing embryo and in the adult.", DEVELOPMENTAL CELL, vol. 12, 2007, pages 181 - 194
"Activation of endothelial cell protease activated receptor 1 by the protein C pathway", SCIENCE, vol. 296, 2002, pages 1880 - 1882
"A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization", CELL, vol. 175, 2018, pages 313 - 326
"Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor", CANCER CELL, vol. 24, 2013, pages 130 - 137
"Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle", SCIENCE, vol. 344, 2014, pages 649 - 652
"Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma", CELL, vol. 152, 2013, pages 1065 - 1076
"VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis", NATURE MEDICINE, vol. 12, 2006, pages 793 - 800
"Dedifferentiation of committed epithelial cells into stem cells in vivo", NATURE, vol. 503, 2013, pages 218 - 223
"Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation", MOLECULAR CANCER, vol. 12, 2013, pages 22
"Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury", NATURE, vol. 517, 2015, pages 621 - 625
"Regenerative activity of the lung after epithelial injury", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1832, 2013, pages 922 - 930
"Hepatocyte TAZ/WWTR1 Promotes Inflammation and Fibrosis in Nonalcoholic Steatohepatitis", CELL, vol. 24, 2016, pages 848 - 862
"Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis", NATURE, vol. 465, 2010, pages 483 - 486
"Endothelial expression of hypoxia-inducible factor 1 protects the murine heart and aorta from pressure overload by suppression of TGF-beta signaling", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 109, 2012, pages E841 - 850
"Hierarchical organization of the hemostatic response to penetrating injuries in the mouse macrovasculature", JOURNAL OF THROMBOSIS AND HAEMOSTASIS: JTH, vol. 15, 2017, pages 526 - 537
"FOXO1 couples metabolic activity and growth state in the vascular endothelium", NATURE, vol. 529, 2016, pages 216 - 220
"Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance", NATURE IMMUNOLOGY, vol. 14, 2013, pages 785 - 792
"Macrophage biology in development, homeostasis and disease", NATURE, vol. 496, 2013, pages 445 - 455
"Mechanisms of fibrosis: therapeutic translation for fibrotic disease", NATURE MEDICINE, vol. 18, 2012, pages 1028 - 1040
"Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury", NATURE MEDICINE, vol. 16, 2010, pages 535 - 543
"Endothelial-to-mesenchymal transition contributes to cardiac fibrosis", NATURE MEDICINE, vol. 13, 2007, pages 952 - 961
"BMP-7 counteracts TGF-betal-induced epithelial-to-mesenchymal transition and reverses chronic renal injury", NAT MED, vol. 9, 2003, pages 964 - 968
"The metabolic regulation of aging", NATURE MEDICINE, vol. 21, 2015, pages 1416 - 1423
"Neutrophils promote alveolar epithelial regeneration by enhancing type II pneumocyte proliferation in a model of acid-induced acute lung injury. American journal of physiology", LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, vol. 311, 2016, pages L1062 - L1075
"Methylation determines fibroblast activation and fibrogenesis in the kidney", NAT MED, vol. 16, 2010, pages 544 - 550
ELPEK GÜLSÜM ÖZLEM: "Neuropilins and liver", WORLD JOURNAL OF GASTROENTEROLOGY, vol. 21, no. 23, 21 June 2015 (2015-06-21), CN , pages 7065 - 7073, XP055944543, ISSN: 1007-9327, DOI: 10.3748/wjg.v21.i23.7065
CAO SHENG, YAQOOB USMAN, DAS AMITAVA, SHERGILL UDAY, JAGAVELU KUMARAVELU, HUEBERT ROBERT C., ROUTRAY CHITTARANJAN, ABDELMONEIM SOH: "Neuropilin-1 promotes cirrhosis of the rodent and human liver by enhancing PDGF/TGF-β signaling in hepatic stellate cells", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 120, no. 7, 1 July 2010 (2010-07-01), GB , pages 2379 - 2394, XP055944547, ISSN: 0021-9738, DOI: 10.1172/JCI41203
WU MING-HENG, CHEN YUH-LING, LEE KUEN-HAUR, CHANG CHE-CHANG, CHENG TSAI-MU, WU SZU-YUAN, TU CHAO-CHIANG, TSUI WAN-LIN: "Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-β- and PDGF-like signals in hepatic stellate cells", SCIENTIFIC REPORTS, vol. 7, no. 1, 1 December 2017 (2017-12-01), pages 1 - 16, XP055944554, DOI: 10.1038/s41598-017-11212-1
MATILLA LARA, ARRIETA VANESSA, JOVER EVA, GARCIA-PEÑA AMAIA, MARTINEZ-MARTINEZ ERNESTO, SADABA RAFAEL, ALVAREZ VIRGINIA, NAVARRO A: "Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1", CELLS, vol. 9, no. 7, pages 1 - 15, XP055944563, DOI: 10.3390/cells9071667
COPPLE BRYAN L., BUSTAMANTE JUAN J., WELCH TIMOTHY P., KIM NAM DEUK, MOON JEON-OK: "Hypoxia-inducible factor-dependent production of profibrotic mediators by hypoxic hepatocytes", LIVER INTERNATIONAL, vol. 29, no. 7, 1 August 2009 (2009-08-01), GB , pages 1010 - 1021, XP055944572, ISSN: 1478-3223, DOI: 10.1111/j.1478-3231.2009.02015.x
SCHIETKE RUTH E., HACKENBECK THOMAS, TRAN MAXINE, GÜNTHER REGINA, KLANKE BERND, WARNECKE CHRISTINA L., KNAUP KARL X., SHUKLA DEEPA: "Renal Tubular HIF-2α Expression Requires VHL Inactivation and Causes Fibrosis and Cysts", PLOS ONE, vol. 7, no. 1, January 2012 (2012-01-01), pages 1 - 12, XP055944576, DOI: 10.1371/journal.pone.0031034
SOPEL MRYANDA J., ROSIN NICOLE L., FALKENHAM ALEC G., BEZUHLY MICHAEL, ESMON CHARLES T., LEE TIMOTHY D. G., LIWSKI ROBERT S., LÉGA: "Treatment with Activated Protein C (aPC) Is Protective during the Development of Myocardial Fibrosis: An Angiotensin II Infusion Model in Mice", PLOS ONE, vol. 7, no. 9, 19 September 2012 (2012-09-19), pages 1 - 10, XP055944577, DOI: 10.1371/journal.pone.0045663
SUZUKI KOJI ET AL: "Protective role of activated protein C in lung and airway remodeling.", CRITICAL CARE MEDICINE, vol. 32, no. 5 Suppl, 1 May 2004 (2004-05-01), US , pages S262 - S265, XP009081045, ISSN: 0090-3493, DOI: 10.1097/01.CCM.0000129668.96935.A8
"Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology", SCIENCE, vol. 357, 2017
"Methylation determines fibroblast activation and fibrogenesis in the kidney", NATURE MEDICINE, vol. 16, 2010, pages 544 - 550
"A vascular niche and a VEGF-Nrpl loop regulate the initiation and sternness of skin tumours", NATURE, vol. 478, 2011, pages 399 - 403
"Platelets: covert regulators of lymphatic development", ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, vol. 30, 2010, pages 2368 - 2371
"Vascular endothelial growth factor-B acts as a coronary growth factor in transgenic rats without inducing angiogenesis, vascular leak, or inflammation", CIRCULATION, vol. 122, 2010, pages 1725 - 1733
"Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity.", CELL METAB, vol. 18, 2013, pages 478 - 489
"Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.", NATURE MEDICINE, vol. 22, 2016, pages 154 - 162
" Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis", SCIENCE TRANSLATIONAL MEDICINE, vol. 9, 2017
"Molecular mechanisms and clinical applications of angiogenesis", NATURE, vol. 473, 2011, pages 298 - 307
"Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity", CANCER CELL, vol. 24, 2013, pages 695 - 709
"Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective", NAT MED, vol. 9, 2003, pages 338 - 342
"Targeting HIF2 in Clear Cell Renal Cell Carcinoma", COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, vol. 81, 2016, pages 113 - 121
"Role of endothelial cell metabolism in vessel sprouting", CELL METAB, vol. 18, 2013, pages 634 - 647
"Macrophage regulation of tumor responses to anticancer therapies", CANCER CELL, vol. 23, 2013, pages 277 - 286
"Alveolar progenitor and stem cells in lung development, renewal and cancer", NATURE, 2014
"Translational strategies and challenges in regenerative medicine", NATURE MEDICINE, vol. 20, 2014, pages 814 - 821
"Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis", NATURE, vol. 505, 2014, pages 97 - 102
"Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration", NATURE, vol. 468, 2010, pages 310 - 315
"Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization", CELL, vol. 147, 2011, pages 539 - 553
"Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1", SCIENCE, vol. 324, 2009, pages 1289 - 1293
"Distinct mechanisms regulate TIMP-1 expression at different stages of phorbol ester-mediated differentiation of U937 cells", BIOCHEMISTRY, vol. 36, 1997, pages 2492 - 2500
"Molecular circuits in thrombosis and inflammation", THROMB HAEMOST, vol. 109, 2013, pages 416 - 420
"Therapy for fibrotic diseases: nearing the starting line", SCIENCE TRANSLATIONAL MEDICINE, vol. 5, no. 167, 2013, pages srl6l
"Infusion of mature megakaryocytes into mice yields functional platelets", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 120, 2010, pages 3917 - 3922
"Migrating Platelets Are Mechano-scavengers that Collect and Bundle Bacteria", CELL, vol. 171, 2017, pages 1368 - 1382
"Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung", CELL, vol. 176, 2019, pages 113 - 126
"Macrophage heterogeneity in tissues: phenotypic diversity and functions", IMMUNOL REV, vol. 262, 2014, pages 36 - 55
"Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins", SCIENCE, vol. 307, 2005, pages 265 - 268
"PARI signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells", NAT MED, vol. 21, 2015, pages 1307 - 1317
"Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance", SCIENCE TRANSLATIONAL MEDICINE, vol. 6, 2014, pages 231ra247
"Targeting of alphav integrin identifies a core molecular pathway that regulates fibrosis in several organs", NATURE MEDICINE, vol. 19, 2013, pages 1617 - 1624
"Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury", NATURE MEDICINE, vol. 15, 2009, pages 384 - 391
"Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function", CELL STEM CELL, vol. 15, 2014, pages 123 - 138
"Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis", NAT MED, vol. 13, 2007, pages 1349 - 1358
"Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes", NATURE MEDICINE, vol. 12, 2006, pages 557 - 567
"Targeting CXCR4-dependent immunosuppressive Ly6Clow monocytes improves antiangiogenic therapy in colorectal cancer", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 114, 2017, pages 10455 - 10460
"Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors", SCIENCE, vol. 344, 2014, pages 630 - 634
"HIF 1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression", NAT REV CANCER, vol. 12, 2011, pages 9 - 22
"Lung regeneration: mechanisms, applications and emerging stem cell populations", NATURE MEDICINE, vol. 20, 2014, pages 822 - 832
"Perivascular Glil+ progenitors are key contributors to injury-induced organ fibrosis", CELL STEM CELL, vol. 16, 2015, pages 51 - 66
"Age-dependent modulation of vascular niches for haematopoietic stem cells", NATURE, vol. 532, 2015, pages 380 - 384
"Aggravation of viral hepatitis by platelet-derived serotonin", NATURE MEDICINE, vol. 14, 2008, pages 756 - 761
"Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy", CELL STEM CELL, vol. 21, 2017, pages 120 - 134
"The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors", NATURE, vol. 544, 2017, pages 105 - 109
"Platelet-derived serotonin mediates liver regeneration", SCIENCE, vol. 312, 2006, pages 104 - 107
"Overexpressing endothelial cell protein C receptor alters the hemostatic balance and protects mice from endotoxin", J THROMB HAEMOST, vol. 3, 2005, pages 1351 - 1359
"WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature", NATURE, vol. 437, 2005, pages 417 - 421
"Platelet-macrophage partnership in innate immunity and inflammation", NATURE IMMUNOLOGY, vol. 14, 2013, pages 768 - 770
"Peptidylarginine deiminase 4 promotes age-related organ fibrosis", THE JOURNAL OF EXPERIMENTAL MEDICINE, vol. 214, 2017, pages 439 - 458
"Pulmonary fibrosis: patterns and perpetrators", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 122, 2012, pages 2756 - 2762
"Platelet-derived SDF-1 primes the pulmonary capillary vascular niche to drive lung alveolar regeneration", NATURE CELL BIOLOGY, vol. 17, 2015, pages 123 - 136
"Functional significance of the platelet immune receptors GPVI and CLEC-2", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 129, 2019, pages 12 - 23
"Endothelium-microenvironment interactions in the developing embryo and in the adult.", DEVELOPMENTAL CELL, vol. 12, 2007, pages 181 - 194
"Activation of endothelial cell protease activated receptor 1 by the protein C pathway", SCIENCE, vol. 296, 2002, pages 1880 - 1882
"A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization", CELL, vol. 175, 2018, pages 313 - 326
"Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor", CANCER CELL, vol. 24, 2013, pages 130 - 137
"Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle", SCIENCE, vol. 344, 2014, pages 649 - 652
"Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma", CELL, vol. 152, 2013, pages 1065 - 1076
"VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis", NATURE MEDICINE, vol. 12, 2006, pages 793 - 800
"Dedifferentiation of committed epithelial cells into stem cells in vivo", NATURE, vol. 503, 2013, pages 218 - 223
"Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation", MOLECULAR CANCER, vol. 12, 2013, pages 22
"Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury", NATURE, vol. 517, 2015, pages 621 - 625
"Regenerative activity of the lung after epithelial injury", BIOCHIMICA ET BIOPHYSICA ACTA, vol. 1832, 2013, pages 922 - 930
"Hepatocyte TAZ/WWTR1 Promotes Inflammation and Fibrosis in Nonalcoholic Steatohepatitis", CELL, vol. 24, 2016, pages 848 - 862
"Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis", NATURE, vol. 465, 2010, pages 483 - 486
"Endothelial expression of hypoxia-inducible factor 1 protects the murine heart and aorta from pressure overload by suppression of TGF-beta signaling", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 109, 2012, pages E841 - 850
"Hierarchical organization of the hemostatic response to penetrating injuries in the mouse macrovasculature", JOURNAL OF THROMBOSIS AND HAEMOSTASIS: JTH, vol. 15, 2017, pages 526 - 537
"FOXO1 couples metabolic activity and growth state in the vascular endothelium", NATURE, vol. 529, 2016, pages 216 - 220
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Attorney, Agent or Firm:
CHONGQING ENZHOU INTELLECTUAL PROPERTY AGENCY (SPECIAL GENERAL PARTNERSHIP) (CN)
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