The TGF-b-induced gene product, big-h3: its biological implications in peritoneal dialysis

Background. TGF-b is involved in peritoneal changes during long-term peritoneal dialysis (PD). TGF-b induces big-h3 in several cell lines, and big-h3 may be a marker for biologically active TGF-b. However, no study has reported induction of big-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 big-h3 during mesothelial cell injury and repair, employing the adhesion, spreading, scratching and cell migration assays. Changes in bigh3 expression after high glucose exposure in vivo were also evaluated using an animal chronic PD model. Results. In vitro, TGF-b1 induced big-h3 in cultured HPMCs, and big-h3-mediated mesothelial cell adhesion occurred via avb3 integrin. big-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, big-h3 concentrations in the dialysate effluent increased in the dialysis group with alterations in peritoneal structure and function during PD, and big-h3 positively correlated with peritoneal solute transport. Immunohistochemical and immunoblotting results showed that big-h3 localizes in the mesothelium and submesothelial matrix of the parietal peritoneum, and in the vascular endothelium of omentum. big-h3 protein expression was higher in the dialysis group. Conclusion. In vitro, big-h3 induced by TGF-b1 in HPMCs improved adhesion and migration of HPMCs during wound healing. In the chronic infusion model of PD, big-h3 played a role in the functional deterioration of the peritoneal membrane, which is associated with fibrosis.