NDT Advance Access originally published online on August 17, 2007
Nephrology Dialysis Transplantation 2008 23(1):126-135; doi:10.1093/ndt/gfm540
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The TGF-β-induced gene product, βig-h3: its biological implications in peritoneal dialysis
1Division of Nephrology and Department of Internal Medicine, 2Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, South Korea
Correspondence to: Yong-Lim Kim, MD, Division of Nephrology and Department of Internal Medicine, Kyungpook National University Hospital, 50 Samduk-dong, Jung-gu, Daegu 700-721, South Korea. Email: ylkim{at}knu.ac.kr
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Abstract |
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Background. TGF-β is involved in peritoneal changes during long-term peritoneal dialysis (PD). TGF-β induces βig-h3 in several cell lines, and βig-h3 may be a marker for biologically active TGF-β. However, no study has reported induction of βig-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 βig-h3 during mesothelial cell injury and repair, employing the adhesion, spreading, scratching and cell migration assays. Changes in βig-h3 expression after high glucose exposure in vivo were also evaluated using an animal chronic PD model.
Results. In vitro, TGF-β1 induced βig-h3 in cultured HPMCs, and βig-h3-mediated mesothelial cell adhesion occurred via 
vβ3 integrin. βig-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, βig-h3 concentrations in the dialysate effluent increased in the dialysis group with alterations in peritoneal structure and function during PD, and βig-h3 positively correlated with peritoneal solute transport. Immunohistochemical and immunoblotting results showed that βig-h3 localizes in the mesothelium and submesothelial matrix of the parietal peritoneum, and in the vascular endothelium of omentum. βig-h3 protein expression was higher in the dialysis group.
Conclusion. In vitro, βig-h3 induced by TGF-β1 in HPMCs improved adhesion and migration of HPMCs during wound healing. In the chronic infusion model of PD, βig-h3 played a role in the functional deterioration of the peritoneal membrane, which is associated with fibrosis.
Keywords: βig-h3; fibrosis; high glucose; mesothelial cells; peritoneum; TGF-β1
Received for publication: 5. 1.07
Accepted in revised form: 17. 7.07
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