Virus-derived serpin reduces immuno-coagulopathic damage in murine colitis by targeting the urokinase-type plasminogen activator receptor (uPAR) and complement.

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In Discovery Literature.

Virus-derived serpin reduces immuno-coagulopathic damage in murine colitis by targeting the urokinase-type plasminogen activator receptor (uPAR) and complement.

Publication date: Dec 19, 2025

A virus-derived serpin, Serp-1, has proven efficacy in treating inflammatory and coagulation disorders in preclinical and clinical studies. Serp-1 evolved over millions of years to block host immune responses, targeting serine proteases in immune and coagulation pathways. Treatment with PEGylated Serp-1 (PEGSerp-1) protein reduced lung injury in both lupus lung hemorrhage and SARS-CoV-2 models. Here, PEGSerp-1 effects on immune-coagulopathic responses is examined in a mouse colitis model. Inflammatory bowel disease (IBD) is associated with life-threatening complications with severe inflammation, bleeding, vasculitis, cancer and toxic megacolon. Serine protease cascades activate coagulation and complement pathways throughout the human body and are regulated by inhibitors, termed serpins, that can reduce gut inflammation. Prophylactic PEGSerp-1 significantly improved survival in severe 5% Dextran sodium sulfate (DSS) colitis, reducing inflammation and crypt damage. Colon damage and inflammation were also reduced after either acute colitis induced by 5% DSS or repeat 2% DSS induced colitis. PEGSerp-1 reduced inflammatory M1 macrophage invasion, urokinase-type plasminogen activator receptor (uPAR), fibrinogen and complement on immunohistochemical analysis. PEGSerp-1 reduced uPAR expression in human macrophage, but not colon cells. Here we report analysis of PEGSerp-1 as a tissue and macrophage targeting therapeutic for colitis, reducing immune and coagulation induced damage in the colon.

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Concepts Keywords
Colitis Coagulation
Host Colitis
Immunohistochemical Colon
Lung Complement
Years Damage
Dss
Immune
Induced
Inflammation
Inflammatory
Pegserp
Reduced
Serp
Targeting
Upar

Semantics

Type Source Name
disease MESH colitis
drug DRUGBANK Serine
disease MESH lung injury
disease MESH hemorrhage
disease MESH Inflammatory bowel disease
pathway KEGG Inflammatory bowel disease
disease MESH inflammation
disease MESH vasculitis
disease MESH cancer
disease MESH toxic megacolon
drug DRUGBANK Dextran
drug DRUGBANK Sodium sulfate
disease MESH DSS
drug DRUGBANK Fibrinogen Human
drug DRUGBANK Urokinase
pathway REACTOME Reproduction
disease MESH included
disease MESH TD2
disease MESH ulcerative colitis
disease MESH genetic susceptibility
disease MESH thrombosis
disease MESH ischemia
disease MESH arterial occlusions
disease MESH heart attacks
disease MESH deep vein thrombosis
drug DRUGBANK Alteplase
drug DRUGBANK Acetylsalicylic acid
disease MESH infection
disease MESH vascular disease
disease MESH osteonecrosis
drug DRUGBANK Azathioprine
drug DRUGBANK Methotrexate
drug DRUGBANK Sphingosine
drug DRUGBANK Phosphate ion
drug DRUGBANK Human C1-esterase inhibitor
drug DRUGBANK Antithrombin III human
disease MESH sepsis
drug DRUGBANK Heparin
drug DRUGBANK Spinosad
disease MESH viral infection
pathway KEGG Viral replication
drug DRUGBANK Thrombin
disease MESH unstable angina
disease MESH arthritis
disease MESH muscular dystrophy
disease MESH uveitis
disease MESH spinal cord injury
drug DRUGBANK Polyethylene glycol
disease MESH weight loss
disease MESH body weight
disease MESH diarrhea
disease MESH weight gain
disease MESH fed
disease MESH injury
drug DRUGBANK Water
drug DRUGBANK Isoxaflutole
drug DRUGBANK L-Arginine
disease MESH cardiovascular disease
disease MESH venous thrombosis
drug DRUGBANK Sulodexide
drug DRUGBANK Trypsin
drug DRUGBANK Chymotrypsin
disease MESH recurrence
drug DRUGBANK Phenobarbital
drug DRUGBANK Sodium lauryl sulfate
disease MESH SDS
disease MESH NHS
disease MESH PBS
disease MESH strains
disease MESH dyspnea
disease MESH lethargy
drug DRUGBANK Pentobarbital
drug DRUGBANK Formaldehyde
pathway REACTOME Apoptosis
disease MESH edema
drug DRUGBANK Ethanol
disease MESH leukemia
disease MESH Rad
drug DRUGBANK Acetate ion
drug DRUGBANK Tromethamine
drug DRUGBANK Lysergic acid diethylamide
disease MESH Papa
disease MESH Dis
disease MESH carcinogenesis
disease MESH acute coronary syndromes
drug DRUGBANK Filgrastim
disease MESH ileitis
disease MESH pouchitis
disease MESH experimental liver cirrhosis
disease MESH dysbiosis
disease MESH myxoma
disease MESH atherosclerotic plaque
disease MESH vascular injury
drug DRUGBANK Guanosine
drug DRUGBANK Naproxen

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