TGF-beta system: the principal profibrotic mediator of peritoneal adhesion formation

Whether induced by infection, inflammation, ischemia, and/or surgical injury, peritoneal adhesions are the leading cause of pelvic pain, bowel obstruction, and infertility. Although some patients develop limited scar tissues, others for unknown reasons develop severe adhesions from seemingly equal procedures. Additionally in the same patient, adhesions develop at one surgical site but not in another. The mechanisms underlying the predisposition to form scars as well as their site specificity are unknown. Because a large number of intraperitoneal surgical procedures are performed each day, many patients are at risk of developing postoperative adhesions. As such, understanding the nature of molecular events and their mechanisms of action is essential, and in the absence of such information, attempts to prevent patients from developing adhesions will remain an empirical process. An unprecedented advancement in surgical techniques have resulted in minimizing peritoneal tissue injury that cause adhesion formation. Increased understanding of the cellular and molecular events that lead to scar tissue formation has also led to the identification of many biologically active molecules with the potential of regulating inflammatory and immune responses, angiogenesis, and tissue remodeling, events that are central to normal peritoneal wound healing and adhesion formation. This article attempts to highlight some of the key molecules (i.e., the transforming growth factor family and its regulatory mechanisms) that are recognized to regulate peritoneal wound repair and adhesion formation. Such understanding of peritoneal biology not only will assist us to better manage patients with adhesions but also will assist those with endometriosis and malignant diseases that affect the peritoneal cavity.