scholarly journals Astragalus membranaceus Inhibits Peritoneal Fibrosis via Monocyte Chemoattractant Protein (MCP)-1 and the Transforming Growth Factor-β1 (TGF-β1) Pathway in Rats Submitted to Peritoneal Dialysis

2014 ◽  
Vol 15 (7) ◽  
pp. 12959-12971 ◽  
Author(s):  
Zhenghong Li ◽  
Lu Zhang ◽  
Weiming He ◽  
Changle Zhu ◽  
Jinsong Yang ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Astragalus Membranaceus ◽  
Peritoneal Fibrosis ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Tgf Β1

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

2018 ◽  
Vol 314 (2) ◽  
pp. F167-F180 ◽  
Author(s):  
Tetsuyoshi Kariya ◽  
Hayato Nishimura ◽  
Masashi Mizuno ◽  
Yasuhiro Suzuki ◽  
Yoshihisa Matsukawa ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Cell Lines ◽  
Transforming Growth Factor ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
Mrna Levels ◽  
Peritoneal Fibrosis ◽  
Ultrafiltration Failure ◽  
Tgf Β1

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-induced VEGF-A was suppressed by TGF-β receptor I (TGFβR-I) inhibitor. Incremental peak values of VEGF-A mRNA stimulated by TGF-β1 in human cultured mesothelial cells derived from PD patients with a range of peritoneal membrane functions correlated with D/P Cr ( P < 0.05). To evaluate the regulatory mechanisms of VEGF-A and neoangiogenesis in vivo, we administered TGFβR-I inhibitor intraperitoneally in a rat chlorhexidine-induced peritoneal injury (CG) model. TGFβR-I inhibitor administration in the CG model decreased peritoneal thickness ( P < 0.001), the number of vessels ( P < 0.001), and VEGF-A levels ( P < 0.05). These results suggest that neoangiogenesis is associated with fibrosis through the TGF-β1-VEGF-A pathway in mesothelial cells and fibroblasts. These findings are important when considering the strategy for management of UFF in PD patients.

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