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- Title
Milk fat globule-EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium.
- Authors
Bu, Heng-Fu; Zuo, Xiu-Li; Wang, Xiao; Ensslin, Michael A; Koti, Vjola; Hsueh, Wei; Raymond, Adam S; Shur, Barry D; Tan, Xiao-Di
- Abstract
Milk fat globule-EGF factor 8 (MFG-E8)/lactadherin participates in several cell surface-mediated regulatory events. Although its mRNA is present in the gut, the physiological roles of MFG-E8 in the intestinal mucosa have not been explored. Here we show that MFG-E8 was expressed in intestinal lamina propria macrophages from mice. Using a wound-healing assay, MFG-E8 was shown to promote the migration of intestinal epithelial cells through a PKCepsilon-dependent mechanism. MFG-E8 bound to phosphatidylserine and triggered reorientation of the actin cytoskeleton in intestinal epithelial cells at the wound edge. Depleting MFG-E8 in mice by administration of anti-MFG-E8 antibody or targeted deletion of the MFG-E8 gene resulted in a slowing of enterocyte migration along the crypt-villus axis and focal mucosal injury. Moreover, in septic mice, intestinal MFG-E8 expression was downregulated, which correlated with intestinal injury, interrupted enterocyte migration, and impaired restitution. Treatment with recombinant MFG-E8 restored enterocyte migration, whereas deletion of MFG-E8 impeded mucosal healing in mice with sepsis. These results suggest that a decrease in intestinal MFG-E8 impairs intestinal mucosal repair in sepsis. Together, our data indicate that MFG-E8 plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing and suggest that recombinant MFG-E8 may be beneficial for the treatment of bowel injuries.
- Subjects
MUSCLE protein metabolism; ANIMAL experimentation; ANTIGENS; BIOLOGICAL models; CELL motility; COMPARATIVE studies; CYTOPLASM; EPITHELIAL cells; HOMEOSTASIS; IMMUNOGLOBULINS; MACROPHAGES; RESEARCH methodology; MEDICAL cooperation; MICE; MILK proteins; PHOSPHOLIPIDS; RATS; RECOMBINANT proteins; RESEARCH; RNA; SEPSIS; TRANSFERASES; WOUND healing; EVALUATION research; CHEMICAL inhibitors
- Publication
Journal of Clinical Investigation, 2007, Vol 117, Issue 12, p3673
- ISSN
0021-9738
- Publication type
journal article