Influence of defunctionalization and mechanical forces on intestinal epithelial wound healing.

The influence on mucosal healing of luminal nutrient flow and the forces it creates are poorly understood. We hypothesized that altered deformation and extracellular pressure mediate, in part, the effects of defunctionalization on mucosal healing. We created patent or partially obstructing defunctionalizing jejunal Roux-en-Y anastomoses in rats to investigate mucosal healing in the absence or presence of luminal nutrient flow and measured luminal pressures to document partial obstruction.

ERK regulates strain-induced migration and proliferation from different subcellular locations.

Repetitive deformation like that engendered by peristalsis or villous motility stimulates intestinal epithelial proliferation on collagenous substrates and motility across fibronectin, each requiring ERK. We hypothesized that ERK acts differently at different intracellular sites. We stably transfected Caco-2 cells with ERK decoy expression vectors that permit ERK activation but interfere with its downstream signaling.

The effects of increased extracellular deformation, pressure, and integrin phosphorylation on fibroblast migration.

Wound healing requires fibroblast migration. Increased pressure slows migration and ulcer healing. Pressure also induces beta1 integrin phosphorylation.

Delineating the signals by which repetitive deformation stimulates intestinal epithelial migration across fibronectin.

Repetitive strain stimulates intestinal epithelial migration across fibronectin via focal adhesion kinase (FAK), Src, and extracellular signal-related kinase (ERK) although how these signals act and interact remains unclear. We hypothesized that PI3K is central to this pathway. We subjected Caco-2 and intestinal epithelial cell-6 cells to 10 cycles/min deformation on flexible fibronectin-coated membranes, assayed migration by wound closure, and signaling by immunoblots.

Supraphysiologic extracellular pressure inhibits intestinal epithelial wound healing independently of luminal nutrient flow.

Background: Luminal pressure may injure the gut mucosa in obstruction, ileus, or inflammatory bowel disease.

Methods: We formed Roux-en-Y anastomoses in 19 mice, creating proximal and defunctionalized partially obstructed limbs and a distal limb to vary luminal pressure and flow. We induced mucosal ulcers by serosal acetic acid, and assessed proliferation (proliferating cell nuclear antigen) and ERK (immunoblotting).

Complications are increased with the need for an abdominal-assisted Kraske procedure.

The Kraske procedure offers a sphincter-saving alternative for surgical correction of rectal disease. This study was performed to investigate the complication rate with the traditional (transsacral) Kraske procedure versus an abdominal-assisted Kraske approach (laparoscopic or open). We conducted a retrospective review of all patients undergoing the Kraske procedure at Harper University Hospital over a 10-year period.