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Transforming growth factor (TGF)\u03b2 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-\u03b21 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 &lt; 0.001) and TGF-\u03b21 ( P &lt; 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 &lt; 0.01) and peritoneal thickness ( P &lt; 0.001). TGF-\u03b21 increased VEGF-A production in human mesothelial cell lines and fibroblast cell lines, and TGF-\u03b21-induced VEGF-A was suppressed by TGF-\u03b2 receptor I (TGF\u03b2R-I) inhibitor. Incremental peak values of VEGF-A mRNA stimulated by TGF-\u03b21 in human cultured mesothelial cells derived from PD patients with a range of peritoneal membrane functions correlated with D\/P Cr ( P &lt; 0.05). To evaluate the regulatory mechanisms of VEGF-A and neoangiogenesis in vivo, we administered TGF\u03b2R-I inhibitor intraperitoneally in a rat chlorhexidine-induced peritoneal injury (CG) model. TGF\u03b2R-I inhibitor administration in the CG model decreased peritoneal thickness ( P &lt; 0.001), the number of vessels ( P &lt; 0.001), and VEGF-A levels ( P &lt; 0.05). These results suggest that neoangiogenesis is associated with fibrosis through the TGF-\u03b21-VEGF-A pathway in mesothelial cells and fibroblasts. These findings are important when considering the strategy for management of UFF in PD patients.<\/jats:p>","DOI":"10.1152\/ajprenal.00052.2017","type":"journal-article","created":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T00:20:13Z","timestamp":1507162813000},"page":"F167-F180","source":"Crossref","is-referenced-by-count":78,"title":["TGF-\u03b21-VEGF-A pathway induces neoangiogenesis with peritoneal fibrosis in patients undergoing peritoneal dialysis"],"prefix":"10.1152","volume":"314","author":[{"given":"Tetsuyoshi","family":"Kariya","sequence":"first","affiliation":[{"name":"Department of Nephrology and Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan"},{"name":"Futatsuya 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