Journal
JOURNAL OF CELL BIOLOGY
Volume 163, Issue 4, Pages 859-869Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200304153
Keywords
chemokines; proliferation; regeneration; duct; interferon
Categories
Funding
- NIDDK NIH HHS [DK55230] Funding Source: Medline
- NIMH NIH HHS [P30 MH062261, R01 MH062231, MH62261, MH62231] Funding Source: Medline
- NINDS NIH HHS [R01 NS036979, NS36979] Funding Source: Medline
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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.
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