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Iatrogenic extracellular matrix disruption as a local trigger for postoperative ileus
Johannes Chang1, Sven Wehner, Nico Schäfer
1Department of General, Visceral, Thoracic, and Vascular Surgery, University of Bonn, Bonn, Germany.
The Journal of Surgical Research
|October 20, 2012
Summary
Matrix metallopeptidase 9 (MMP-9) and hyaluronan contribute to postoperative ileus by disrupting the extracellular matrix. Inhibiting MMP-9 may offer a new treatment for this condition.
Area of Science:
- Gastroenterology
- Inflammation Research
- Surgical Complications
Background:
- Matrix metallopeptidase 9 (MMP-9) actively disrupts the extracellular matrix (ECM), contributing to inflammatory disorders.
- Postoperative ileus involves intestinal inflammation, potentially triggered by MMP-9 and hyaluronan, an ECM breakdown product.
Purpose of the Study:
- To investigate the inflammatory role of MMP-9 and hyaluronan in triggering postoperative ileus.
- To explore the potential of MMP-9 inhibition as a therapeutic strategy for postoperative ileus.
Main Methods:
- Standardized intestinal surgery in rats to induce ileus, assessed via fluorescein isothiocyanate-dextran transit assay.
- Analysis of intestinal muscularis for mRNA expression of IL-6, MMP-9, and CD44.
- Quantification of peritoneal MMP-9 activity, peritoneal fluid and serum hyaluronan, and tissue inhibitor of metalloproteinase 1 using zymography and ELISA.
- Culture of peritoneal macrophages stimulated with postsurgical peritoneal fluid or hyaluronan to assess IL-6 and macrophage inflammatory protein-1α release.
Main Results:
- Surgical manipulation significantly delayed intestinal transit.
- Induced expression of IL-6, MMP-9, and CD44 mRNAs in jejunal and colonic muscularis.
- Elevated MMP-9 activity, hyaluronan, and tissue inhibitor of metalloproteinase 1 in peritoneal fluid and serum.
- Postsurgical peritoneal fluid and hyaluronan stimulated peritoneal macrophages to release higher levels of IL-6 and macrophage inflammatory protein-1α.
Conclusions:
- MMP-9-mediated ECM disruption and hyaluronan release, coupled with CD44 receptor induction, can initiate proinflammatory cascades causing postoperative ileus.
- Matrix metallopeptidase 9 inhibition presents a promising therapeutic avenue for managing postoperative ileus.
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