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
Rok vydání: 2007
Předmět:
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