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Research ArticleGastroenterology Free access | 10.1172/JCI31841

Milk fat globule–EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium

Heng-Fu Bu,1 Xiu-Li Zuo,1,2 Xiao Wang,1 Michael A. Ensslin,3 Vjola Koti,1 Wei Hsueh,4 Adam S. Raymond,3 Barry D. Shur,3 and Xiao-Di Tan1

1Molecular and Cellular Pathobiology Program and Center for Digestive Disease and Immunobiology, Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2Department of Gastroenterology, Qilu Hospital, Medical College of Shandong University, Jinan, Shandong, People’s Republic of China. 3Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA. 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Address correspondence to: Xiao-Di Tan, Molecular and Cellular Pathobiology Program, Children’s Memorial Research Center, Children’s Memorial Hospital, 2300 Children’s Plaza, Box 217, Chicago, Illinois 60614, USA. Phone: (773) 755-6380; Fax: (773) 755-6581; E-mail: xtan@northwestern.edu.

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1Molecular and Cellular Pathobiology Program and Center for Digestive Disease and Immunobiology, Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2Department of Gastroenterology, Qilu Hospital, Medical College of Shandong University, Jinan, Shandong, People’s Republic of China. 3Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA. 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Address correspondence to: Xiao-Di Tan, Molecular and Cellular Pathobiology Program, Children’s Memorial Research Center, Children’s Memorial Hospital, 2300 Children’s Plaza, Box 217, Chicago, Illinois 60614, USA. Phone: (773) 755-6380; Fax: (773) 755-6581; E-mail: xtan@northwestern.edu.

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1Molecular and Cellular Pathobiology Program and Center for Digestive Disease and Immunobiology, Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2Department of Gastroenterology, Qilu Hospital, Medical College of Shandong University, Jinan, Shandong, People’s Republic of China. 3Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA. 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Address correspondence to: Xiao-Di Tan, Molecular and Cellular Pathobiology Program, Children’s Memorial Research Center, Children’s Memorial Hospital, 2300 Children’s Plaza, Box 217, Chicago, Illinois 60614, USA. Phone: (773) 755-6380; Fax: (773) 755-6581; E-mail: xtan@northwestern.edu.

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1Molecular and Cellular Pathobiology Program and Center for Digestive Disease and Immunobiology, Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2Department of Gastroenterology, Qilu Hospital, Medical College of Shandong University, Jinan, Shandong, People’s Republic of China. 3Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA. 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Address correspondence to: Xiao-Di Tan, Molecular and Cellular Pathobiology Program, Children’s Memorial Research Center, Children’s Memorial Hospital, 2300 Children’s Plaza, Box 217, Chicago, Illinois 60614, USA. Phone: (773) 755-6380; Fax: (773) 755-6581; E-mail: xtan@northwestern.edu.

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1Molecular and Cellular Pathobiology Program and Center for Digestive Disease and Immunobiology, Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2Department of Gastroenterology, Qilu Hospital, Medical College of Shandong University, Jinan, Shandong, People’s Republic of China. 3Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA. 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Address correspondence to: Xiao-Di Tan, Molecular and Cellular Pathobiology Program, Children’s Memorial Research Center, Children’s Memorial Hospital, 2300 Children’s Plaza, Box 217, Chicago, Illinois 60614, USA. Phone: (773) 755-6380; Fax: (773) 755-6581; E-mail: xtan@northwestern.edu.

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1Molecular and Cellular Pathobiology Program and Center for Digestive Disease and Immunobiology, Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2Department of Gastroenterology, Qilu Hospital, Medical College of Shandong University, Jinan, Shandong, People’s Republic of China. 3Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA. 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Address correspondence to: Xiao-Di Tan, Molecular and Cellular Pathobiology Program, Children’s Memorial Research Center, Children’s Memorial Hospital, 2300 Children’s Plaza, Box 217, Chicago, Illinois 60614, USA. Phone: (773) 755-6380; Fax: (773) 755-6581; E-mail: xtan@northwestern.edu.

Find articles by Hsueh, W. in: PubMed | Google Scholar

1Molecular and Cellular Pathobiology Program and Center for Digestive Disease and Immunobiology, Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2Department of Gastroenterology, Qilu Hospital, Medical College of Shandong University, Jinan, Shandong, People’s Republic of China. 3Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA. 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Address correspondence to: Xiao-Di Tan, Molecular and Cellular Pathobiology Program, Children’s Memorial Research Center, Children’s Memorial Hospital, 2300 Children’s Plaza, Box 217, Chicago, Illinois 60614, USA. Phone: (773) 755-6380; Fax: (773) 755-6581; E-mail: xtan@northwestern.edu.

Find articles by Raymond, A. in: PubMed | Google Scholar

1Molecular and Cellular Pathobiology Program and Center for Digestive Disease and Immunobiology, Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2Department of Gastroenterology, Qilu Hospital, Medical College of Shandong University, Jinan, Shandong, People’s Republic of China. 3Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA. 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Address correspondence to: Xiao-Di Tan, Molecular and Cellular Pathobiology Program, Children’s Memorial Research Center, Children’s Memorial Hospital, 2300 Children’s Plaza, Box 217, Chicago, Illinois 60614, USA. Phone: (773) 755-6380; Fax: (773) 755-6581; E-mail: xtan@northwestern.edu.

Find articles by Shur, B. in: PubMed | Google Scholar

1Molecular and Cellular Pathobiology Program and Center for Digestive Disease and Immunobiology, Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. 2Department of Gastroenterology, Qilu Hospital, Medical College of Shandong University, Jinan, Shandong, People’s Republic of China. 3Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA. 4Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Address correspondence to: Xiao-Di Tan, Molecular and Cellular Pathobiology Program, Children’s Memorial Research Center, Children’s Memorial Hospital, 2300 Children’s Plaza, Box 217, Chicago, Illinois 60614, USA. Phone: (773) 755-6380; Fax: (773) 755-6581; E-mail: xtan@northwestern.edu.

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Published November 15, 2007 - More info

J Clin Invest. https://doi.org/10.1172/JCI31841.
© 2007 The American Society for Clinical Investigation
Published November 15, 2007 - Version history
Received: February 15, 2007; Accepted: September 13, 2007
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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 PKCε-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.

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Version history
  • Version 1 (November 15, 2007): No description
  • Version 3 (December 3, 2007): No description
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