NDT Advance Access published online on August 17, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm540
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The TGF-ß-induced gene product, ßig-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 and offprint requests 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-ß is involved in peritoneal changes during long-term peritoneal dialysis (PD). TGF-ß induces ßig-h3 in several cell lines, and ßig-h3 may be a marker for biologically active TGF-ß. However, no study has reported induction of ßig-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 ßig-h3 during mesothelial cell injury and repair, employing the adhesion, spreading, scratching and cell migration assays. Changes in ßig-h3 expression after high glucose exposure in vivo were also evaluated using an animal chronic PD model.
Results. In vitro, TGF-ß1 induced ßig-h3 in cultured HPMCs, and ßig-h3-mediated mesothelial cell adhesion occurred via 
vß3 integrin. ßig-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, ßig-h3 concentrations in the dialysate effluent increased in the dialysis group with alterations in peritoneal structure and function during PD, and ßig-h3 positively correlated with peritoneal solute transport. Immunohistochemical and immunoblotting results showed that ßig-h3 localizes in the mesothelium and submesothelial matrix of the parietal peritoneum, and in the vascular endothelium of omentum. ßig-h3 protein expression was higher in the dialysis group.
Conclusion. In vitro, ßig-h3 induced by TGF-ß1 in HPMCs improved adhesion and migration of HPMCs during wound healing. In the chronic infusion model of PD, ßig-h3 played a role in the functional deterioration of the peritoneal membrane, which is associated with fibrosis.
Keywords: ßig-h3; fibrosis; high glucose; mesothelial cells; peritoneum; TGF-ß1
Received for publication: 5. 1.07
Accepted in revised form: 17. 7.07
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