Indomethacin and retinoic acid modify mouse intestinal inflammation and fibrosis: a role for SPARC
Autor: | Cynthia Forrest, Borut Klopcic, Ian C. Lawrance, Amber Appelbee, James C. I. Jooste, Warren Sean Raye, Frances Lloyd |
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Rok vydání: | 2007 |
Předmět: |
medicine.medical_specialty
Physiology Ratón Indomethacin Retinoic acid Inflammation Tretinoin digestive system Statistics Nonparametric Extracellular matrix Immunoenzyme Techniques chemistry.chemical_compound Mice Random Allocation Indometacin Crohn Disease Fibrosis Internal medicine medicine Extracellular Animals Osteonectin biology Reverse Transcriptase Polymerase Chain Reaction Gastroenterology medicine.disease digestive system diseases Disease Models Animal Endocrinology chemistry Trinitrobenzenesulfonic Acid Enzyme inhibitor Immunology biology.protein RNA Female medicine.symptom medicine.drug |
Zdroj: | Digestive diseases and sciences. 53(6) |
ISSN: | 0163-2116 |
Popis: | The mouse model of 2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)-induced intestinal fibrosis allows for detailed study of the extracellular matrix changes that complicate Crohn's disease. Indomethacin induces intesti- nal fibrosis, while retinoic acid (RA) reduces liver fibrosis. Secreted protein acidic and rich in cysteine (SPARC), an extracellular matrix-modifying agent, may potentially link these opposing effects. Our aim was to determine the effects of indomethacin and RA and to evaluate their cor- relation to SPARC expression in the TNBS mouse model. CD-1 mice were randomised to TNBS enemas weekly for 2 or 8 weeks with or without indomethacin (0.2 mg/kg per day) or RA (100 lg/kg per day). At 2 weeks, indometha- cin/TNBS enhanced and RA reduced inflammation, tissue destruction and fibrosis. The expression of SPARC was inversely related to fibrosis, but not to inflammation, in the TNBS-alone groups at 2 weeks; these differences were lost by 8 weeks. The results demonstrate that indomethacin increases TNBS-induced fibrosis in mice, while RA redu- ces it, and that SPARC may link these opposing effects. |
Databáze: | OpenAIRE |
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