The stromal cell-derived factor-1α/CXCR4 ligand-receptor axis is critical for progenitor survival and migration in the pancreas

Ayse G. Kayali, Kurt Van Gunst, Iain L. Campbell, Aleksandr Stotland, Marcie Kritzik, Guoxun Liu, Malin Flodström-Tullberg, You Qing Zhang, Nora Sarvetnick

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

The SDF-1α/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-1α and CXCR4 expression in fetal pancreas. We have found that SDF-1α 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) γ-nonobese diabetic mouse. We show that SDF-1α stimulates the phosphorylation of Akt, mitogen-activated protein kinase, and Src in pancreatic duct cells. Furthermore, migration assays indicate a stimulatory effect of SDF-1α on ductal cell migration. Importantly, blocking the SDF-1α/CXCR4 axis in IFNγ-nonobese diabetic mice resulted in diminished proliferation and increased apoptosis in the pancreatic ductal cells. Together, these data indicate that the SDF-1α-CXCR4 ligand receptor axis is an obligatory component in the maintenance of duct cell survival, proliferation, and migration during pancreatic regeneration.

Original languageEnglish (US)
Pages (from-to)859-869
Number of pages11
JournalJournal of Cell Biology
Volume163
Issue number4
DOIs
Publication statusPublished - Nov 24 2003

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Keywords

  • Chemokines
  • Duct
  • Interferon
  • Proliferation
  • Regeneration

ASJC Scopus subject areas

  • Cell Biology

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