Human Reproduction, Vol. 16, No. 6, 1291-1300,
June 2001
© 2001 European Society of Human Reproduction and Embryology
Differential expression of TGF-ß1 and TGF-ß3 in serosal tissues of human intraperitoneal organs and peritoneal adhesions*
1 Department of Obstetrics and Gynecology, University of Florida, Gainesville, 2 Wayne State University, Detroit, USA, 3 Department of Surgery, Gothenburg University, Sweden and 4 Genzyme Corporation, Cambridge, MA, USA
Elevated local expression of transforming growth factor (TGF-ß) has been associated with increased incidence of peritoneal adhesion formation. In this study we determine whether differences in basal expression of TGF-ß in serosal tissue of peritoneal organs correlate with incidence of adhesion formation. Serosal tissue of parietal peritoneum, uterus, oviduct, ovary, omentum, large and small bowels as well as adhesions, skin, fascia, subcutaneous tissue, peritoneal fluid and serum were collected from 57 subjects with/without adhesions who were undergoing abdominal/pelvic surgery. To determine TGF-ß1 and TGF-ß3 mRNA and protein expression, total RNA and protein were isolated from these tissues and along with the fluids, subjected to quantitative RT–PCR and enzyme-linked immunosorbent assay (ELISA) respectively. Tissue sections were immunostained for TGF-ß1 and TGF-ß3 protein. We found that TGF-ß1 and TGF-ß3 mRNA and protein are expressed in these tissues and present in peritoneal fluids and serum, with considerable variations in level of their expression. Comparatively, there was more variation in TGF-ß1 than TGF-ß3 expression without age or gender relation. Adhesions express a significantly higher TGF-ß1 mRNA and have the highest TGF-ß1:TGF-ß3 ratio, with lowest concentrations and ratio detected in omentum, small and large bowels; in contrast uterus expresses higher TGF-ß3, with lowest concentrations detected in subcutaneous tissue and large bowels (P < 0.05). A similar trend was also observed for total (active + latent) TGF-ß1 protein expression, with low active TGF-ß1 that was not significantly different among the tissue extracts and fluids. However, the lowest active:total TGF-ß1 ratio was found in adhesions and ovary. In subjects with adhesions, the adhesions express significantly more TGF-ß1 compared to parietal peritoneum (P < 0.05). Immunoreactive TGF-ß1 and TGF-ß3 protein were present in various cell types in these tissues with intensity reflecting their mRNA and protein expression. In conclusion, we provided evidence that serosal tissue of various peritoneal organs and adhesions express TGF-ß1 and TGF-ß3. Since TGF-ß is expressed differently in these tissues and tissue injury often alters the expression of TGF-ß, we propose that tissues with a higher basal expression of TGF-ß may become predisposed to develop more adhesions compared to others.
Key words: fibrotic disorder/inflammatory immune response/peritoneal adhesion/TGF-ß1/TGF-ß3
5 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, University of Florida, College of Medicine, Box 100294, Gainesville, FL 32610–0294, USA. E-mail: cheginin{at}obgyn.ufl.edu
* This paper was presented in part at the 47th Annual Meeting of the Society for Gynecological Investigation, Chicago, IL, USA, 2000.