{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nKNG1, which encodes high‐molecular‐weight kininogen (HK), is a multifunctional precursor protein whose proteolytic processing releases bioactive peptides—most notably bradykinin—and generates two‐chain HK (HKa) containing a critical domain 5. These cleavage products have been implicated in diverse vascular and tumor‐related processes. For example, bradykinin released from HK serves as a chemoattractant and modulator of endothelial cell function, thereby promoting glioma cell invasion toward blood vessels, while HKa and its domain 5 possess antiangiogenic and antiadhesive properties that suppress endothelial proliferation and metastasis. Such actions underscore a dual role for KNG1‐derived peptides in both stimulating and, conversely, inhibiting vascular remodeling and tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its vascular and anti‐tumor roles, HK is a key participant in the intrinsic coagulation cascade and thromboinflammatory processes. Genetic association studies have linked KNG1 variants to alterations in activated partial thromboplastin time (aPTT) and risk for thrombosis, diabetic nephropathy, and changes in adiponectin levels. At the molecular level, HK interacts with plasma enzymes such as prekallikrein, factor XI, and components of the contact system, thereby modulating coagulation, platelet–leukocyte adhesion, and, ultimately, thrombus formation. Together, these findings indicate that KNG1‐derived proteins not only serve as pivotal mediators of hemostasis and fibrinolysis but also influence broader metabolic and vascular risk profiles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, HK and its derived fragments contribute to the regulation of immune responses and host–pathogen interactions. Peptides mapped to domain 5 of HK display antimicrobial activity, modulate platelet and leukocyte adhesion, and affect processes such as efferocytosis by engaging receptors like uPAR on immune cells. In pathogenic settings, microorganisms—including certain bacteria and fungi—bind HK at their surface to manipulate the host’s fibrinolytic and inflammatory cascades, while altered urinary secretion of HK has been observed in renal cell carcinoma and acute kidney injury. Similar disturbances in bradykinin‐mediated signaling are implicated in COVID‐19 pathophysiology, further expanding the spectrum of HK’s (KNG1’s) immunomodulatory functions and its potential as a diagnostic biomarker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "38"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kusumam Joseph, Baby G Tholanikunnel, Allen P Kaplan "}, {"type": "b", "children": [{"type": "t", "text": "Heat shock protein 90 catalyzes activation of the prekallikrein-kininogen complex in the absence of factor XII."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.022626899"}], "href": "https://doi.org/10.1073/pnas.022626899"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11792853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11792853"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Triantafyllos Chavakis, Nicole Boeckel, Sentot Santoso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of platelet adhesion and aggregation by a defined region (Gly-486-Lys-502) of high molecular weight kininogen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M202529200"}], "href": "https://doi.org/10.1074/jbc.M202529200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11970955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11970955"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Narayanan Parthasarathy, Suzy V Torti, Frank M Torti "}, {"type": "b", "children": [{"type": "t", "text": "Ferritin binds to light chain of human H-kininogen and inhibits kallikrein-mediated bradykinin release."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20011637"}], "href": "https://doi.org/10.1042/BJ20011637"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12071855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12071855"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Triantafyllos Chavakis, Robin A Pixley, Irma Isordia-Salas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel antithrombotic role for high molecular weight kininogen as inhibitor of plasminogen activator inhibitor-1 function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M204010200"}], "href": "https://doi.org/10.1074/jbc.M204010200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12082110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12082110"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chien-Da Huang, Omar Tliba, Reynold A Panettieri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bradykinin induces interleukin-6 production in human airway smooth muscle cells: modulation by Th2 cytokines and dexamethasone."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2002-0040OC"}], "href": "https://doi.org/10.1165/rcmb.2002-0040OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12594059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12594059"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yong M Zhu, Dawn A Bradbury, Linhua Pang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of interleukin (IL)-8 by bradykinin in human airway smooth muscle cells involves prostanoid-dependent activation of AP-1 and nuclear factor (NF)-IL-6 and prostanoid-independent activation of NF-kappaB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M301785200"}], "href": "https://doi.org/10.1074/jbc.M301785200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12748173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12748173"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Annie Zhao, Jane-L Lew, Li Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human kininogen gene is transactivated by the farnesoid X receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M304568200"}], "href": "https://doi.org/10.1074/jbc.M304568200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12761213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12761213"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Dian J Cao, Yan-Lin Guo, Robert W Colman "}, {"type": "b", "children": [{"type": "t", "text": "Urokinase-type plasminogen activator receptor is involved in mediating the apoptotic effect of cleaved high molecular weight kininogen in human endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.RES.0000126567.75232.46"}], "href": "https://doi.org/10.1161/01.RES.0000126567.75232.46"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15044324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15044324"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Izabella Z A Pawluczyk, Samita R Patel, Kevin P G Harris "}, {"type": "b", "children": [{"type": "t", "text": "The role of bradykinin in the antifibrotic actions of perindoprilat on human mesangial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1523-1755.2004.00494.x"}], "href": "https://doi.org/10.1111/j.1523-1755.2004.00494.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15086463"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15086463"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yi Wu, Victor Rizzo, Yuchuan Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kininostatin associates with membrane rafts and inhibits alpha(v)beta3 integrin activation in human umbilical vein endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.107.148759"}], "href": "https://doi.org/10.1161/ATVBAHA.107.148759"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17585065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17585065"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Lan G Coffman, Derek Parsonage, Ralph D'Agostino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulatory effects of ferritin on angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0812010106"}], "href": "https://doi.org/10.1073/pnas.0812010106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19126685"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19126685"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Vedrana Montana, Harald Sontheimer "}, {"type": "b", "children": [{"type": "t", "text": "Bradykinin promotes the chemotactic invasion of primary brain tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.3825-10.2011"}], "href": "https://doi.org/10.1523/JNEUROSCI.3825-10.2011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21451024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21451024"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jinfang Xu, Jun Fang, Zhonghao Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of the Kininogen-1 inhibits proliferation and induces apoptosis of glioma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-018-0833-0"}], "href": "https://doi.org/10.1186/s13046-018-0833-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30068373"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30068373"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "R A Pixley, Y Lin, I Isordia-Salas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fine mapping of the sequences in domain 5 of high molecular weight kininogen (HK) interacting with heparin and zinc."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1538-7836.2003.00291.x"}], "href": "https://doi.org/10.1046/j.1538-7836.2003.00291.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12911595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12911595"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Triantafyllos Chavakis, Sentot Santoso, Kenneth J Clemetson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High molecular weight kininogen regulates platelet-leukocyte interactions by bridging Mac-1 and glycoprotein Ib."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M304344200"}], "href": "https://doi.org/10.1074/jbc.M304344200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12952972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12952972"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Masayasu Kawasaki, Toshinaga Maeda, Kazuyoshi Hanasawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of His-Gly-Lys motif derived from domain 5 of high molecular weight kininogen on suppression of cancer metastasis both in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308790200"}], "href": "https://doi.org/10.1074/jbc.M308790200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14506238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14506238"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Dawn A Bradbury, Robert Newton, Yong M Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclooxygenase-2 induction by bradykinin in human pulmonary artery smooth muscle cells is mediated by the cyclic AMP response element through a novel autocrine loop involving endogenous prostaglandin E2, E-prostanoid 2 (EP2), and EP4 receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M307964200"}], "href": "https://doi.org/10.1074/jbc.M307964200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14517215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14517215"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Lawrence P Fernando, Snehlatha Natesan, Kusumam Joseph, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High molecular weight kininogen and factor XII binding to endothelial cells and astrocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH03-04-0231"}], "href": "https://doi.org/10.1160/TH03-04-0231"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14597972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14597972"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Emma Andersson Nordahl, Victoria Rydengård, Matthias Mörgelin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Domain 5 of high molecular weight kininogen is antibacterial."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M507249200"}], "href": "https://doi.org/10.1074/jbc.M507249200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16091369"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16091369"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Nathalie Vionnet, David Tregouët, Gbenga Kazeem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of 14 candidate genes for diabetic nephropathy on chromosome 3q in European populations: strongest evidence for association with a variant in the promoter region of the adiponectin gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db06-0271"}], "href": "https://doi.org/10.2337/db06-0271"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17065357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17065357"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "J Scharfstein, V Schmitz, E Svensjö, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kininogens coordinate adaptive immunity through the proteolytic release of bradykinin, an endogenous danger signal driving dendritic cell maturation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Scand J Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-3083.2007.01983.x"}], "href": "https://doi.org/10.1111/j.1365-3083.2007.01983.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17635790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17635790"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Maria P Canter, Carol A Graham, Michael H Heit, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic techniques identify urine proteins that differentiate patients with interstitial cystitis from asymptomatic control subjects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Obstet Gynecol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajog.2008.01.052"}], "href": "https://doi.org/10.1016/j.ajog.2008.01.052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18455532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18455532"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "J J Brugts, M P M de Maat, E Boersma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The rationale and design of the PERindopril GENEtic association study (PERGENE): a pharmacogenetic analysis of angiotensin-converting enzyme inhibitor therapy in patients with stable coronary artery disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Drugs Ther (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10557-008-6156-1"}], "href": "https://doi.org/10.1007/s10557-008-6156-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19082699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19082699"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Roland Bechtloff, Andreas Goette, Alicja Bukowska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gender and age-dependent differences in the bradykinin-degradation within the pericardial fluid of patients with coronary artery disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cardiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijcard.2009.06.028"}], "href": "https://doi.org/10.1016/j.ijcard.2009.06.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19592120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19592120"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Nona Sotoodehnia, Guo Li, Catherine O Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation in angiotensin-converting enzyme-related pathways associated with sudden cardiac arrest risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Heart Rhythm (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.hrthm.2009.06.013"}], "href": "https://doi.org/10.1016/j.hrthm.2009.06.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19716087"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19716087"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Sydney C W Tang, Loretta Y Y Chan, Joseph C K Leung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bradykinin and high glucose promote renal tubular inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nephrol Dial Transplant (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/ndt/gfp599"}], "href": "https://doi.org/10.1093/ndt/gfp599"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19923143"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19923143"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Lorna M Houlihan, Gail Davies, Albert Tenesa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common variants of large effect in F12, KNG1, and HRG are associated with activated partial thromboplastin time."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2010.02.016"}], "href": "https://doi.org/10.1016/j.ajhg.2010.02.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20303064"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20303064"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Ying Wu, Yun Li, Ethan M Lange, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study for adiponectin levels in Filipino women identifies CDH13 and a novel uncommon haplotype at KNG1-ADIPOQ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddq423"}], "href": "https://doi.org/10.1093/hmg/ddq423"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20876611"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20876611"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Pierre-Emmanuel Morange, Tiphaine Oudot-Mellakh, William Cohen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KNG1 Ile581Thr and susceptibility to venous thrombosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-11-319053"}], "href": "https://doi.org/10.1182/blood-2010-11-319053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21270443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21270443"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Elizabeth C Murphy, Matthias Mörgelin, Jakki C Cooney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of Bacteroides fragilis and Bacteroides thetaiotaomicron with the kallikrein-kinin system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Microbiology (Reading) (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1099/mic.0.046862-0"}], "href": "https://doi.org/10.1099/mic.0.046862-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21527472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21527472"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Maria Sabater-Lleal, Angel Martinez-Perez, Alfonso Buil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide association study identifies KNG1 as a genetic determinant of plasma factor XI Level and activated partial thromboplastin time."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.112.248492"}], "href": "https://doi.org/10.1161/ATVBAHA.112.248492"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22701019"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22701019"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Bengt Sennblad, Saonli Basu, Johanna Mazur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study with additional genetic and post-transcriptional analyses reveals novel regulators of plasma factor XI levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw401"}], "href": "https://doi.org/10.1093/hmg/ddw401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28053049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28053049"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Kusumam Joseph, Baby G Tholanikunnel, Anette Bygum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Factor XII-independent activation of the bradykinin-forming cascade: Implications for the pathogenesis of hereditary angioedema types I and II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2013.03.026"}], "href": "https://doi.org/10.1016/j.jaci.2013.03.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23672780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23672780"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Shannon L Taylor, Victoria Wahl-Jensen, Anna Maria Copeland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial cell permeability during hantavirus infection involves factor XII-dependent increased activation of the kallikrein-kinin system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1003470"}], "href": "https://doi.org/10.1371/journal.ppat.1003470"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23874198"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23874198"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "C Suffritti, A Zanichelli, L Maggioni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Allergy (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cea.12293"}], "href": "https://doi.org/10.1111/cea.12293"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24552232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24552232"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Aizhen Yang, Jihong Dai, Zhanli Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High molecular weight kininogen binds phosphatidylserine and opsonizes urokinase plasminogen activator receptor-mediated efferocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1302590"}], "href": "https://doi.org/10.4049/jimmunol.1302590"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24688027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24688027"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Vanessa Sandim, Denise de Abreu Pereira, Dário Eluan Kalume, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic analysis reveals differentially secreted proteins in the urine from patients with clear cell renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Urol Oncol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.urolonc.2015.07.016"}], "href": "https://doi.org/10.1016/j.urolonc.2015.07.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26420021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26420021"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Laura Gonzalez-Calero, Marta Martin-Lorenzo, Angeles Ramos-Barron, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Urinary Kininogen-1 and Retinol binding protein-4 respond to Acute Kidney Injury: predictors of patient prognosis?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep19667"}], "href": "https://doi.org/10.1038/srep19667"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26792617"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26792617"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Joseph A Roche, Renuka Roche "}, {"type": "b", "children": [{"type": "t", "text": "A hypothesized role for dysregulated bradykinin signaling in COVID-19 respiratory complications."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.202000967"}], "href": "https://doi.org/10.1096/fj.202000967"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32359101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32359101"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Michael W Henderson, Erica M Sparkenbaugh, Shaobin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasmin-mediated cleavage of high-molecular-weight kininogen contributes to acetaminophen-induced acute liver failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood.2020006198"}], "href": "https://doi.org/10.1182/blood.2020006198"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33827130"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33827130"}]}]}]}