Adhesion formation and fibrosis represent a major complication of surgical intervention. Reducing the morbidity associated with adhesions requires an understanding of the mechanisms underlying their formation. Since increased levels of transforming growth factor-β1 (TGFβ1) have been associated with inflammation and adhesion production, we investigated the requirement of TGFβ1 in peritoneal adhesion formation utilizing mice carrying a targeted disruption of the TGFβ1 allele. Mice that were either wild-type (+/+), containing two normal alleles of TGFβ1, or heterozygous (+/-) for the TGFβ1 null allele received injections of magnesium silicate (talc), and the extent of abdominal adhesions was determined utilizing a standard grading score. Wild-type (+/+) animals had at least twofold more TGFβ1 protein in peritoneal fluids at 2 h posttrauma compared to heterozygous (+/-) mice (727 vs. 243 pg TGFβ1/mg protein by enzyme-linked immunosorbent assay (ELISA) in +/+ and +/- mice, respectively), and had significantly less scar and adhesion formation (p < .05) at 7 days posttrauma(1.8 ± 0.8 vs. 3.4 ± 1.4, graded from 0 to 5, in +/+ and +/- mice, respectively). These results demonstrate that haploid insufficiency in TGFβ1 levels can lead to inappropriate matrix and adhesion production during inflammation, and together with previous studies suggest that any perturbation of normal TGFβ1 levels can modulate the injury response that regulates the extent of adhesion formation.
All Science Journal Classification (ASJC) codes
- ELISA analysis
- Surgical adhesions
- Transforming growth factor-β1
- Transgenic mice