Possible involvement of SDF-1alpha/CXCR4-DPPIV axis in TGF-beta1-induced enhancement of migratory potential in human peritoneal mesothelial cells

Cell Tissue Res. 2007 Nov;330(2):221-9. doi: 10.1007/s00441-007-0455-x. Epub 2007 Sep 11.


We have previously reported that human peritoneal mesothelial cells (HPMCs) express a large amount of dipeptidyl peptidase IV (DPPIV) and that its expression is regulated by a variety of bioactive substances in malignant ascites from ovarian cancer patients. The aim of this study has been to examine the expression and role of the SDF-1alpha/CXCR4-DPPIV axis in HPMCs. We have demonstrated that the expression levels of DPPIV and E-cadherin in HPMCs decrease, following TGF-beta1-induced morphological change, in a time- and concentration-dependent manner. Additionally, we show that both SDF-1alpha (a chemokine and substrate for DPPIV) and its receptor, CXCR4, are expressed on HPMCs, and that their expression levels are upregulated by TGF-beta1 treatment, resulting in an increased migratory potential of HPMCs. Furthermore, the migratory potential of HPMCs is significantly enhanced in the presence of SDF-1alpha or DPPIV-specific inhibitor in the wound-healing assay. These results suggest that DPPIV and SDF-1alpha/CXCR4 play crucial roles in regulating the migratory potential of HPMCs, which may be involved in the re-epithelialization of denuded basement membrane at the site of peritoneal injury.

MeSH terms

  • Basement Membrane / drug effects
  • Basement Membrane / metabolism
  • Cadherins / drug effects
  • Cadherins / metabolism
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cells, Cultured
  • Chemokine CXCL12 / metabolism*
  • Dipeptidyl Peptidase 4 / drug effects
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelium / metabolism
  • Humans
  • Peritoneum / cytology
  • Peritoneum / metabolism*
  • Receptors, CXCR4 / metabolism*
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta1 / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • Wound Healing / drug effects
  • Wound Healing / physiology


  • Cadherins
  • Chemokine CXCL12
  • Receptors, CXCR4
  • Transforming Growth Factor beta1
  • Dipeptidyl Peptidase 4