Coincidence of connective tissue growth factor expression with fibrosis and angiogenesis in postoperative peritoneal adhesion formation.
OBJECTIVE
To investigate the relationship between connective tissue growth factor (CTGF) and fibrosis and angiogenesis in postoperative peritoneal adhesion formation.


METHODS
Adhesions were performed in 35 rats by creation of a peritoneal patch. Animals were sacrificed at 7 different time-points over 3 weeks. Adhesions and uninjured peritoneum from all animals were assessed by Northern blotting for CTGF and collagen-I mRNA and by immunohistochemistry for CTGF localization, degree of fibrosis and angiogenesis.


RESULTS
Persistent adhesions formed in all animals. CTGF and collagen-I mRNA were increased in adhesions compared to uninjured peritoneum (p < 0.05 for both). The temporal expression pattern depicted delayed peak levels of collagen-I mRNA with increasing tendency for both transcripts at the end of the observation period. Fibrosis within adhesions correlated positively with time after surgery (r = 0.85; p < 0.001) and showed typical signs of chronic tissue fibrosis at later time points. Angiogenesis was detected in adhesions but not in uninjured peritoneum (p = 0.001) and coincided with the spatial and temporal expression of CTGF protein in fibroblasts and vascular endothelial cells.


CONCLUSIONS
The co-expression of CTGF with increasing fibrosis and angiogenesis in postoperative peritoneal adhesions suggests a role for CTGF as critical molecule in fibrous adhesive disease and target for future adhesion prevention.
Thaler
K
K
Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL 33331, USA.
Mack
Judith A
JA
Berho
Mariana
M
Grotendorst
G
G
Wexner
S D
SD
Abramson
Susan R
SR
D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D005355:Fibrosis / Q000473:pathology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic; D010537:Peritoneum / Q000098:blood supply / Q000166:cytology / Q000473:pathology; D011184:Postoperative Period; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000473:pathology*
C526317:CCN2 protein, human; C526316:CCN2 protein, rat; D024042:Collagen Type I; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor