Temporal expression of TGF-beta1, EGF, and PDGF-BB in a model of colonic wound healing.
BACKGROUND
Dehiscence of colonic anastomoses is a multifactorial phenomenon. One mechanism by which this can occur is a deficiency of colonic submucosal collagen. Peptide growth factors (PGFs) have been shown to play a role in the synthesis, deposition, and maturation of collagen. Specifically, in tissues other than the colon, the transforming growth factor-beta (TGF-beta1) gene has been shown to be temporally associated with expression of the procollagen gene. This study examines the temporal expression of the TGF-beta1, epidermal growth factor (EGF), and platelet-derived growth factor B (PDGF-BB) genes and their temporal relationship to the expression of the procollagen type 1 (PROC I) gene.


METHODS
Forty-eight Sprague-Dawley rats underwent transection of the descending colon with primary anastomosis. Perianastomotic colonic tissue was harvested on Day 0 and postoperative days 3, 5, 6, 7, and 14. Colonic tissue was analyzed using semiquantitative reverse transcriptase-polymerase chain reaction and primers specific for the TGF-beta1, EGF, and PDGF-B growth factors. Relative expression ratios of PGFs and PROC I genes were calculated versus a constitutive gene.


RESULTS
The data show that although all three of the PGFs genes were expressed in healing postoperative colonic tissue, only TGF-beta1 showed a significant increase in its level of expression versus a constitutive gene from a mean ratio of 0.4 +/- 0. 08 on Day 0 to a mean ratio of 1.9 +/- 0.27 on Day 7 (P < 0.0001 by ANOVA). The PROC I gene also showed a significant increase in expression (P < 0.001 by ANOVA) in the postoperative period which temporally correlated with the increase in the expression of the TGF-beta1 gene (r = 0.89, P < 0.05).


CONCLUSIONS
The temporal correlation between an increase in the gene expression of TGF-beta1 and PROC I is initial evidence that that TGF-beta1 plays a significant role in collagen metabolism in a healing colonic anastomosis.
Buckmire
M A
MA
Philadelphia Veterans Administration Medical Center, Medical College of Pennsylvania/Hahnemann University, Philadelphia, Pennsylvania, 19102-1192, USA.
Parquet
G
G
Greenway
S
S
Rolandelli
R H
RH
D000818:Animals; D000077214:Becaplermin; D003106:Colon / Q000293:injuries*; D004815:Epidermal Growth Factor / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011347:Procollagen / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014945:Wound Healing / Q000502:physiology*; D014950:Wounds, Penetrating / Q000503:physiopathology*
D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D000077214:Becaplermin; D004815:Epidermal Growth Factor