Expression of connective tissue growth factor in intra-abdominal adhesions.
OBJECTIVE
Connective tissue growth factor stimulates fibroblast proliferation and extracellular matrix deposition in many fibrotic disorders. The aim of our study was to determine the expression pattern of connective tissue growth factor in postoperative intra-abdominal adhesions.


METHODS
Adhesions were created in 46 Sprague-Dawley rats by complete dissection and resuturing of a peritoneal patch 2 cm in diameter, lateral from the midline incision. Animals were killed at postoperative Days 3, 6, 9, 12, 15, 18, and 21 and the adhesions scored on a scale of 0 to 5. Tissue samples from adhesion areas and from uninvolved peritoneum were evaluated by Northern and Western blotting for temporal connective tissue growth factor mRNA and protein expression, respectively. Immunohistochemical analysis was performed for connective tissue growth factor localization.


RESULTS
Adhesions formed in all animals after surgery and were confined to the peritoneal patches. Adhesion formation increased across time, with significant correlation between adhesion scores and postoperative days (r = 0.329, P = 0.026). Connective tissue growth factor mRNA concentrations were significantly elevated in adhesion tissue throughout the three-week period when compared with normal peritoneum (P = 0.012); peak levels occurred between Days 6 and 15. Western blots demonstrated connective tissue growth factor protein expression in adhesions from Days 6 to 21, in contrast to negligible bands in normal peritoneum. Fibroblasts within the adhesive tissue, but not in uninjured peritoneum, stained positive for connective tissue growth factor by immunohistochemistry.


CONCLUSIONS
We have demonstrated a specific temporal and spatial expression pattern for connective tissue growth factor in intra-abdominal adhesions during a three-week postoperative time course. According to what is known about the functional role of connective tissue growth factor in fibrogenesis, our findings warrant further investigations addressing a causal relationship between this growth factor and fibrous adhesion formation.
Thaler
Klaus
K
Department of Colorectal Surgery, Cleveland Clinic-Florida, 2950 Cleveland Clinic Boulevard, Weston, FL 33331, USA.
Mack
Judith A
JA
Zhao
Rong Hua
RH
Berho
Mariana
M
Grotendorst
Gary R
GR
Duncan
Matthew R
MR
Williams
Shawn
S
Miranda
Julianne R
JR
Wexner
Steven D
SD
Abramson
Susan R
SR
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D055513:Connective Tissue Growth Factor; D004195:Disease Models, Animal; D005767:Gastrointestinal Diseases / Q000378:metabolism* / Q000601:surgery; D017874:Immediate-Early Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D011183:Postoperative Complications; D011184:Postoperative Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000209:etiology / Q000378:metabolism
C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor