TGF-β1-VEGF-A pathway induces neoangiogenesis with peritoneal fibrosis in patients undergoing peritoneal dialysis

The characteristic features of chronic peritoneal injury with peritoneal dialysis (PD) are submesothelial fibrosis and neoangiogenesis. Transforming growth factor (TGF)β and vascular endothelial growth factor (VEGF)-A are the main mediators of fibrosis and neoangiogenesis, respectively; however, the effect of the interaction between them on the peritoneum is not well known. In this study, we investigated the relationship between TGF-β1 and VEGF-A in inducing peritoneal fibrosis by use of human tissues and dialysate, cultured cells, and animal models. The VEGF-A concentration correlated with the dialysate-to-plasma ratio of creatinine (D/P Cr) (P < 0.001) and TGF-β1 (P < 0.001) in human PD effluent. VEGF-A mRNA levels increased significantly in the peritoneal tissues of human ultrafiltration failure (UFF) patients and correlated with number of vessels (P < 0.01) and peritoneal thickness (P < 0.001). TGF-β1 increased VEGF-A production in human mesothelial cell lines and fibroblast cell lines, and TGF-β1-ind...