Tuesday, 31 May 2011

Mucosal defense : Restitution

The critical first task following disruption of the gastrointestinal epithelium is to cover the denuded area and re-establish the intrinsic barrier. This rapid restoration of epithelium is accomplished by a process called restitution - epithelial cells adjacent to the defect flatten and migrate over the exposed basement membrane. In the small intestine, this process is aided by a rapid contraction and shortening of the affected villi, which reduces the area of basement membrane that must be covered.

Restitution provides a rapid mechanism for covering a defect in the barrier and does not involve proliferation of epithelial cells. It results in an area that, while protected, is not physiologically functional. Healing requires that the epithelial cells on the margins of the defect proliferate, differentiate and migrate into the damaged area to restore the normal cellular architecture and function.

Restitution has been shown to be stimulated by a number of mostly paracrine regulators. Local prostaglandins and trefoil proteins are clearly involved in this process, and suppression of their production significantly delays restitution. Another group of molecules involved in restitution is the polyamines such as spermine, spermidine and putrescine. These molecules are present in many diets and also synthesized by the gastrointestinal mucosa. Enteral administration of polyamines has been shown in experimental models to accelerate restitution and healing of mucosal lesions.

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