Intestinal Interstitial Edema

Intestinal interstitial edema is often associated with abdominal surgery and trauma resuscitation.  However, despite the association of edema with dysfunction in many systems, interstitial edema, the accumulation of fluid in the interstitium, is often thought of as a side effect of therapy after surgery or abdominal trauma.

We have developed a model of intestinal edema to study the signal transduction mechanisms mediating edema-induced dysfunction.  This animal model allows us to study the molecular mechanisms of edema induced dysfunction along with functional outcomes such as intestinal transit, contractile activity, and permeability.  We have shown that intestinal edema slows intestinal transit by decreasing intestinal contractile activity via decreased myosin light chain phosphorylation.  We hypothesize that a mechanical signal such as increased cell stretch or increased fluid flux through the tissue triggers a signaling cascade that results in decreased myosin light chain phosphorylation.

In addition to the animal model, we have developed a primary intestinal smooth muscle cell model.  Using a combination of the animal and cell models, we have discovered that both STAT3 and NFkappaB are activated in intestinal edema.  Furthermore, cadherin mediated cell-cell adhesion appears to be altered. We are currently studying the interaction between these signaling pathways, the mechanical signal triggered by edema development, and how these signaling pathways result in decreased myosin light chain phosphorylation.  Our current understanding of signaling mechanisms involved in edema-induced intestinal dysfunction.