AJP - Gastrointestinal and Liver Physiology, Vol 257, Issue 2 274-G283, Copyright © 1989 by American Physiological Society

ARTICLES

Villus contraction aids repair of intestinal epithelium after injury

R. Moore, S. Carlson and J. L. Madara
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachussets 02115.

A highly reproducible in vitro model of intestinal epithelial injury in guinea pig ileum was used to study the structural and functional events that accompany rapid epithelial repair. This model is characterized by denudation of the villus tip followed by rapid restitution of the epithelial barrier. Using standard electrophysiological and quantitative morphometric techniques, we found that immediately after injury the number of cells lost exceeded the number of empty cell positions on the denuded basement membrane by 100%. Concurrently, cytoplasmic processes of subepithelial myofibroblasts contained condensations of microfilaments that were not apparent in controls. Additionally, villus height was diminished immediately after injury, and progressively decreased during the restitution period. In tissues that were depleted of ATP using the uncoupler dinitrophenol and in tissues functionally denervated by tetrodotoxin, villus shortening after injury was significantly reduced. Denervation also retarded functionally and structurally defined reestablishment of epithelial barrier function. These data suggest that intestinal epithelial repair is aided by energy-dependent, neurally mediated villus contraction. We speculate that the subepithelial network of myofibroblasts is responsible for this process, which effectively minimizes the denuded surface area to be reepithelialized.

This article has been cited by other articles:

				A. T. Blikslager, A. J. Moeser, J. L. Gookin, S. L. Jones, and J. Odle Restoration of Barrier Function in Injured Intestinal Mucosa Physiol Rev, April 1, 2007; 87(2): 545 - 564. [Abstract] [Full Text] [PDF]

				N. B. Campbell, C. G. Ruaux, D. E. Shifflett, J. M. Steiner, D. A. Williams, and A. T. Blikslager Physiological concentrations of bile salts inhibit recovery of ischemic-injured porcine ileum Am J Physiol Gastrointest Liver Physiol, August 1, 2004; 287(2): G399 - G407. [Abstract] [Full Text] [PDF]

				T. Chitapanarux, S. L. Chen, H. Lee, A. C. Melton, and H. F. Yee Jr. C-type natriuretic peptide induces human colonic myofibroblast relaxation Am J Physiol Gastrointest Liver Physiol, January 1, 2004; 286(1): G31 - G36. [Abstract] [Full Text] [PDF]

				J. L. Gookin, J. A. Galanko, A. T. Blikslager, and R. A. Argenzio PG-mediated closure of paracellular pathway and not restitution is the primary determinant of barrier recovery in acutely injured porcine ileum Am J Physiol Gastrointest Liver Physiol, November 1, 2003; 285(5): G967 - G979. [Abstract] [Full Text] [PDF]

				B. C. McKaig, D. McWilliams, S. A. Watson, and Y. R. Mahida Expression and Regulation of Tissue Inhibitor of Metalloproteinase-1 and Matrix Metalloproteinases by Intestinal Myofibroblasts in Inflammatory Bowel Disease Am. J. Pathol., April 1, 2003; 162(4): 1355 - 1360. [Abstract] [Full Text] [PDF]

				D. Little, R. A. Dean, K. M. Young, S. A. McKane, L. D. Martin, S. L. Jones, and A. T. Blikslager PI3K signaling is required for prostaglandin-induced mucosal recovery in ischemia-injured porcine ileum Am J Physiol Gastrointest Liver Physiol, January 1, 2003; 284(1): G46 - G56. [Abstract] [Full Text] [PDF]

				J. L. Gookin, J. M. Rhoads, and R. A. Argenzio Inducible nitric oxide synthase mediates early epithelial repair of porcine ileum Am J Physiol Gastrointest Liver Physiol, July 1, 2002; 283(1): G157 - G168. [Abstract] [Full Text] [PDF]

				A T Blikslager, D N Zimmel, K M Young, N B Campbell, D Little, and R A Argenzio Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2 Gut, May 1, 2002; 50(5): 615 - 623. [Abstract] [Full Text] [PDF]

				L E Kernochan, B N Tran, P Tangkijvanich, A C Melton, S P Tam, and H F Yee Jr Endothelin-1 stimulates human colonic myofibroblast contraction and migration Gut, January 1, 2002; 50(1): 65 - 70. [Abstract] [Full Text] [PDF]

				W. Li, A. Duzgun, B. E. Sumpio, and M. D. Basson Integrin and FAK-mediated MAPK activation is required for cyclic strain mitogenic effects in Caco-2 cells Am J Physiol Gastrointest Liver Physiol, January 1, 2001; 280(1): G75 - G87. [Abstract] [Full Text] [PDF]

				J.-Y. Wang, J. Wang, V. A. Golovina, L. Li, O. Platoshyn, and J. X.-J. Yuan Role of K+ channel expression in polyamine-dependent intestinal epithelial cell migration Am J Physiol Cell Physiol, February 1, 2000; 278(2): C303 - C314. [Abstract] [Full Text] [PDF]

				D. B. Polk and W. Tong Epidermal and hepatocyte growth factors stimulate chemotaxis in an intestinal epithelial cell line Am J Physiol Cell Physiol, December 1, 1999; 277(6): C1149 - C1159. [Abstract] [Full Text] [PDF]

				D. W. Powell, R. C. Mifflin, J. D. Valentich, S. E. Crowe, J. I. Saada, and A. B. West Myofibroblasts. II. Intestinal subepithelial myofibroblasts Am J Physiol Cell Physiol, August 1, 1999; 277(2): C183 - C201. [Abstract] [Full Text] [PDF]

				D. W. Powell, R. C. Mifflin, J. D. Valentich, S. E. Crowe, J. I. Saada, and A. B. West Myofibroblasts. I. Paracrine cells important in health and disease Am J Physiol Cell Physiol, July 1, 1999; 277(1): C1 - C19. [Abstract] [Full Text] [PDF]

				B. C. McKaig, S. S. Makh, C. J. Hawkey, D. K. Podolsky, and Y. R. Mahida Normal human colonic subepithelial myofibroblasts enhance epithelial migration (restitution) via TGF-beta 3 Am J Physiol Gastrointest Liver Physiol, May 1, 1999; 276(5): G1087 - G1093. [Abstract] [Full Text] [PDF]

				O. Han, G. D. Li, B. E. Sumpio, and M. D. Basson Strain induces Caco-2 intestinal epithelial proliferation and differentiation via PKC and tyrosine kinase signals Am J Physiol Gastrointest Liver Physiol, September 1, 1998; 275(3): G534 - G541. [Abstract] [Full Text] [PDF]