Medical College of Wisconsin
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Mucosal angiogenesis regulation by CXCR4 and its ligand CXCL12 expressed by human intestinal microvascular endothelial cells. Am J Physiol Gastrointest Liver Physiol 2004 Jun;286(6):G1059-68

Date

02/07/2004

Pubmed ID

14764445

DOI

10.1152/ajpgi.00417.2003

Scopus ID

2-s2.0-2642545685 (requires institutional sign-in at Scopus site)   67 Citations

Abstract

Mice genetically deficient in the chemokine receptor CXCR4 or its ligand stromal cell-derived factor (SDF)-1/CXCL12 die perinatally with marked defects in vascularization of the gastrointestinal tract. The aim of this study was to define the expression and angiogenic functions of microvascular CXCR4 and SDF-1/CXCL12 in the human intestinal tract. Studies of human colonic mucosa in vivo and primary cultures of human intestinal microvascular endothelial cells (HIMEC) in vitro showed that the intestinal microvasculature expresses CXCR4 and its cognate ligand SDF-1/CXCL12. Moreover, SDF-1/CXCL12 stimulation of HIMEC triggers CXCR4-linked G proteins, phosphorylates ERK1/2, and activates proliferative and chemotactic responses. Pharmacological studies indicate SDF-1/CXCL12 evokes HIMEC chemotaxis via activation of ERK1/2 and phosphoinositide 3-kinase signaling pathways. Consistent with chemotaxis and proliferation, endothelial tube formation was inhibited by neutralizing CXCR4 or SDF-1/CXCL12 antibodies, as well as the ERK1/2 inhibitor PD-98059. Taken together, these data demonstrate an important mechanistic role for CXCR4 and SDF-1/CXCL12 in regulating angiogenesis within the human intestinal mucosa.

Author List

Heidemann J, Ogawa H, Rafiee P, Lügering N, Maaser C, Domschke W, Binion DG, Dwinell MB

Author

Michael B. Dwinell PhD Center Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Biocompatible Materials
Cell Division
Chemokine CXCL12
Chemokines, CXC
Chemotaxis
Collagen
Drug Combinations
Endothelium, Vascular
Humans
Intestinal Mucosa
Laminin
Ligands
Microcirculation
Mitogen-Activated Protein Kinases
Neovascularization, Physiologic
Phosphorylation
Proteoglycans
Receptors, CXCR4