Abstract
Preservation of structural and functional integrity of the intestinal mucosa depends on its ability to defend itself from noxious luminal agents and to effect repair when injury occurred. Coordinated healing of mucosal injury in the intestine is determined by depth of injury and dynamic balance between ongoing destructive and reparative mechanisms. Repair after intestinal injury usually involves a cascade of events: up-regulation of the immune system, leukocyte accumulation and activation, stimulation of cell migration, proliferation, and differentiation. Angiogenesis and extracellular matrix formation also contribute to mucosal tissue remodeling. Re-estabHshing epithelial surface continuity is the first requirement of mucosal wound healing. This is initially accomplished by rapid migration of intestinal epithelial cells from the wound margin, a process termed restitution. Restitution prevents deeper mucosal damage and effects closure of shallow defects of the mucosal epithelium within minutes to hours, a much shorter time frame than that required for cell proHferation [1-3]. Cell migration depends on coordinated extension of lamellopodia and filopodia, formation and breaking of focal contacts at the leading edge of the cell as well as cytoskeletalmediated retraction at the trailing edge [4, 5]. Following restitution, cell proliferation accomplishes replacement of lost epithelial cell populations. While resealing surface epithelial continuity is a first priority, injury associated with inflammatory bowel diseases and other intestinal disorders is typically accompanied by deeper damage. The processes which reconstitute normal intestinal architecture in the context of transmural inflammatory injury remain incompletely understood. However, the heterogeneous populations of connective tissue fibroblasts, myofibroblasts and smooth muscle cells, as well as other cell types present in the intestine, also make substantial contributions to mucosal wound healing. Of note, eventual down-regulation of the inflammatory responses associated with mucosal injury is necessary to prevent pathological fibrosis which may lead to the clinical manifestations of intestinal stenosis or stricture formation. Recent research has improved understanding of the factors regulating mucosal wound healing in the intestine. This progress has been made possible largely by use of in-vitro cell culture models as well as chemically and genetically induced animal models. This chapter summarizes recent advances in understanding of the regulation of mucosal repair processes as well as intrinsic protective key mechanisms essential for maintaining mucosal surface integrity and normal mucosal function in the intestine.
Original language | English (US) |
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Title of host publication | Inflammatory Bowel Disease |
Subtitle of host publication | From Bench to Bedside |
Publisher | Springer US |
Pages | 197-209 |
Number of pages | 13 |
ISBN (Print) | 0387258078, 9788847004337 |
DOIs | |
State | Published - 2006 |
ASJC Scopus subject areas
- General Medicine