The TGF-β-induced gene product, βig-h3: Its biological implications in peritoneal dialysis

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 αvβ3 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.