Document Type

Article

Journal Title

The Journal of cell biology

Publication Date

11-24-2003

Volume

163

Abstract

The SDF-1alpha/CXCR4 ligand/chemokine receptor pair is required for appropriate patterning during ontogeny and stimulates the growth and differentiation of critical cell types. Here, we demonstrate SDF-1alpha and CXCR4 expression in fetal pancreas. We have found that SDF-1alpha and its receptor CXCR4 are expressed in islets, also CXCR4 is expressed in and around the proliferating duct epithelium of the regenerating pancreas of the interferon (IFN) gamma-nonobese diabetic mouse. We show that SDF-1alpha stimulates the phosphorylation of Akt, mitogen-activated protein kinase, and Src in pancreatic duct cells. Furthermore, migration assays indicate a stimulatory effect of SDF-1alpha on ductal cell migration. Importantly, blocking the SDF-1alpha/CXCR4 axis in IFNgamma-nonobese diabetic mice resulted in diminished proliferation and increased apoptosis in the pancreatic ductal cells. Together, these data indicate that the SDF-1alpha-CXCR4 ligand receptor axis is an obligatory component in the maintenance of duct cell survival, proliferation, and migration during pancreatic regeneration.

MeSH Headings

Animals, Apoptosis, Cell Division, Cell Movement, Cell Survival, Cells, Cultured, Chemokine CXCL12, Chemokines, CXC, Disease Models, Animal, Epithelial Cells, Fetus, Ligands, Mice, Mice, Inbred NOD, Mice, Transgenic, Mitogen-Activated Protein Kinases, Pancreas, Pancreatic Ducts, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Receptors, CXCR4, Regeneration, Stem Cells, src-Family Kinases

ISSN

0021-9525

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