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1998 Abstract: THE ROLE OF TRANSFORMING GROWTH FACTOR BETA-1 (TGF-_1) IN PERITONITIS-INDUCED ADHESIONS. A. M. Ghellai, N. Chegini, Q. Dou1, J.M. Kaseta2, J.W. Burns2, K.C. Skinner2, A. F. Stucchi and J.M. Becker, Department of Surgery, Boston University School of Medicine, Boston, MA; 2Genzyme Corporation, Cambridge, MA and 1Institute for Wound Research, University of Florida, Gainesville, FL. 85

Abstracts
1998 Digestive Disease Week

#989

THE ROLE OF TRANSFORMING GROWTH FACTOR BETA-1 (TGF-_1) IN PERITONITIS-INDUCED ADHESIONS. A. M. Ghellai, N. Chegini, Q. Dou1, J.M. Kaseta2, J.W. Burns2, K.C. Skinner2, A. F. Stucchi and J.M. Becker, Department of Surgery, Boston University School of Medicine, Boston, MA; 2Genzyme Corporation, Cambridge, MA and 1Institute for Wound Research, University of Florida, Gainesville, FL.

Peritonitis results in significant intra-abdominal adhesion formation with an associated high morbidity. TGF-_1, a potent chemoattractant, stimulates collagen and fibronectin synthesis by fibroblasts and may play a role in the formation of adhesions. Hence, we hypothesized that TGF-_1 would be upregulated in peritonitis and may contribute to adhesion formation. To test this hypothesis, peritonitis was induced in rats by cecal ligation and puncture while controls were sham operated. Adhesions were scored and harvested from both groups at days 0, 1, 2, 4, and 7. Expression of TGF-_1 m-RNA was determined by quantitative reverse transcriptase polymerase chain reactions normalized to _-actin. Peritonitis was associated with a significantly greater incidence of abdominal adhesions compared with shams. Peritonitis also resulted in a significant increase in the expression of TGF-_1 mRNA at days 2, 4 and 7 with a 9-fold peak on day 4 compared with shams (Table). Immunohistochemical detection of TGF-_1 protein in adhesions also reached maximum by day 4 and subsided by day 7 further supporting the expression of TGF-_1 mRNA. These results suggest that peritonitis is associated with upregulation of TGF-_1 which may exacerbate adhesion formation.

    Time

Number of Adhesions

TGF-_1 mRNA Levels

 

Sham

Treated

Sham

Treated

    Day 0

0

0

0.9 ± 0.3

0.9 ± 0.3

    Day 1

0

8.0 ± 1.6*

0.5 ± 0.3

0

    Day 2

0

8.0 ± 0.5*

1.0 ± 0.2

5.8 ± 1.4*u

    Day 4

0

9.8 ± 1.1*

1.4 ± 0.2

13 ± 1.8*u

    Day 7

0

10.5 ± 1.1*

1.0 ± 0.3

3.0 ± 0.4*u

    Mean ± SEM

*p _ 0.05 compared with day 0
u
p _ 0.05 compared with sham

This research was funded, in part, by the Genzyme Corporation, Cambridge MA.

Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.


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