Possible involvement of SDF-1alpha/CXCR4-DPPIV axis in TGF-beta1-induced enhancement of migratory potential in human peritoneal mesothelial cells.
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.
Kajiyama
Hiroaki
H
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya, 466-8550, Japan. kajiyama@med.nagoya-u.ac.jp
Shibata
Kiyosumi
K
Ino
Kazuhiko
K
Nawa
Akihiro
A
Mizutani
Shigehiko
S
Kikkawa
Fumitaka
F
D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D015820:Cadherins / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D015820:Cadherins; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D053773:Transforming Growth Factor beta1; D018819:Dipeptidyl Peptidase 4