The TGF-beta-induced gene product, betaig-h3: its biological implications in peritoneal dialysis.
BACKGROUND
TGF-beta is involved in peritoneal changes during long-term peritoneal dialysis (PD). TGF-beta induces betaig-h3 in several cell lines, and betaig-h3 may be a marker for biologically active TGF-beta. However, no study has reported induction of betaig-h3 in human peritoneal mesothelial cells (HPMCs) or its involvement in PD-related peritoneal membrane changes.


METHODS
We used cultured HPMCs to investigate the biological roles of betaig-h3 during mesothelial cell injury and repair, employing the adhesion, spreading, scratching and cell migration assays. Changes in betaig-h3 expression after high glucose exposure in vivo were also evaluated using an animal chronic PD model.


RESULTS
In vitro, TGF-beta1 induced betaig-h3 in cultured HPMCs, and betaig-h3-mediated mesothelial cell adhesion occurred via alphavbeta3 integrin. betaig-h3 enhanced mesothelial cell adhesion and migration and, in part, wound healing during mesothelial cell injury. The animal study demonstrated that compared to the control group, betaig-h3 concentrations in the dialysate effluent increased in the dialysis group with alterations in peritoneal structure and function during PD, and betaig-h3 positively correlated with peritoneal solute transport. Immunohistochemical and immunoblotting results showed that betaig-h3 localizes in the mesothelium and submesothelial matrix of the parietal peritoneum, and in the vascular endothelium of omentum. betaig-h3 protein expression was higher in the dialysis group.


CONCLUSIONS
In vitro, betaig-h3 induced by TGF-beta1 in HPMCs improved adhesion and migration of HPMCs during wound healing. In the chronic infusion model of PD, betaig-h3 played a role in the functional deterioration of the peritoneal membrane, which is associated with fibrosis.
Park
Sun-Hee
SH
Division of Nephrology and Department of Internal Medicine, Kyungpook National University School of Medicine, Jung-gu, Daegu, South Korea.
Choi
Soon-Youn
SY
Kim
Mi-Hyung
MH
Oh
Eun-Joo
EJ
Ryu
Hye Myung
HM
Kim
Chan-Duck
CD
Kim
In-San
IS
Kim
Yong-Lim
YL
D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology*; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein