Differential Expression of Matrix Metalloproteinase and Tissue Inhibitor of MMP in Serosal Tissue of Intraperitoneal Organs and Adhesions

Objective: To comparatively analyse the expression of matrix metalloproteinase (MMP-3) and tissue inhibitor of MMP (TIMP-2) in serosal tissue of intraperitoneal organs and adhesions, as well as peritoneal fluid and serum of subjects with and without adhesions.

Design: Cross sectional study.

Setting: Academic research centres.

Sample: Patients undergoing abdominal/pelvic surgery.

Methods: Messenger ribonucleic acid (mRNA) and protein expression using quantitative reverse transcription polymerase chain reaction (Q-RT-PCR), ELISA and immunohistochemistry.

Results: All the tissues examined express MMP-3 and TIMP-2 mRNA and protein at consistently varying levels ranging from 100- to 1000-fold and 2- to 10-fold mRNA and protein, respectively. Serosa of uterine, fallopian tube, ovary and partial peritoneum express a higher MMP-3 mRNA compared with small and large bowels and omentum, while TIMP-2 expression was less variable with the highest level found in uterine serosa (P < 0.05). The expression of MMP-3 and TIMP-2 mRNA in adhesions was not significantly different compared with parietal peritoneum. MMP-3 and TIMP-2 protein content in tissue extracts, peritoneal fluids and serum also varied with higher TIMP-2 than MMP-3 (P < 0.05). TIMP-2 levels were lower in serum of subjects with moderate/extensive adhesions compared with subjects without adhesions. Immunoreactive MMP-3 and TIMP-2 proteins were detected in various cell types in these tissues. There was no correlation between MMP-3 and TIMP-2 expression, and age, gender or menstrual status of subjects with or without adhesions.

Conclusion: MMP-3 and TIMP-2 are expressed at varying levels in serosal tissues of peritoneal organs and adhesions, with higher TIMP-2 than MMP-3. Based on the knowledge that tissue injury alters the expression of MMPs and TIMPs, such variations may predispose an organ to develop more adhesions than others. In addition, the results suggest that serum level of TIMP-2 may represent a marker for subjects who will form adhesions with greater severity.