MicroRNA-302c modulates peritoneal dialysis-associated fibrosis by targeting connective tissue growth factor.

Long-term peritoneal dialysis (PD) can lead to the induction of mesothelial/epithelial-mesenchymal transition (MMT/EMT) and fibrosis; these effects eventually result in ultrafiltration failure and the discontinuation of PD. MicroRNA-302c (miR-302c) is believed to be involved in regulating tumour cell growth and metastasis by suppressing MMT, but the effect of miR-302c on MMT in the context of PD is unknown. MiR-302c levels were measured in mesothelial cells isolated from the PD effluents of continuous ambulatory peritoneal dialysis patients. After miR-302c overexpression using lentivirus, human peritoneal mesothelial cell line (HMrSV5) and PD mouse peritoneum were treated with TGF-β1 or high glucose peritoneal dialysate respectively. MiR-302c expression level and MMT-related factors alteration were observed. In addition, fibrosis of PD mouse peritoneum was alleviated by miR-302c overexpression. Furthermore, the expression of connective tissue growth factor (CTGF) was negatively related by miR-302c, and LV-miR-302c reversed the up-regulation of CTGF induced by TGF-β1. These data suggest that there is a novel TGF-β1/miR-302c/CTGF pathway that plays a significant role in the process of MMT and fibrosis during PD. MiR-302c might be a potential biomarker for peritoneal fibrosis and a novel therapeutic target for protection against peritoneal fibrosis in PD patients.

Li X ，Liu H ，Sun L ，Zhou X ，Yuan X ，Chen Y ，Liu F ，Liu Y ，Xiao L ... -  《-》

Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate.

Mizutani M ，Ito Y ，Mizuno M ，Nishimura H ，Suzuki Y ，Hattori R ，Matsukawa Y ，Imai M ，Oliver N ，Goldschmeding R ，Aten J ，Krediet RT ，Yuzawa Y ，Matsuo S ... -  《-》

MicroRNA-145 promotes the epithelial-mesenchymal transition in peritoneal dialysis-associated fibrosis by suppressing fibroblast growth factor 10.

Peritoneal fibrosis is a common complication of long-term peritoneal dialysis (PD) and the principal cause of ultrafiltration failure during PD. The initial and reversible step in PD-associated peritoneal fibrosis is the epithelial-mesenchymal transition (EMT). Although the mechanisms in the EMT have been the focus of many studies, only limited information is currently available concerning microRNA (miRNA) regulation in peritoneal fibrosis. In this study, we aimed to characterize the roles of microRNA-145 (miR-145) and fibroblast growth factor 10 (FGF10) in peritoneal fibrosis. After inducing EMT with transforming growth factor-β1 (TGF-β1) in vitro, we found that miR-145 is significantly up-regulated, whereas FGF10 is markedly down-regulated, suggesting a close link between miR-145 and FGF10 in peritoneal fibrosis, further confirmed in luciferase reporter experiments. Furthermore, in human peritoneal mesothelial cells (i.e. HMrSV5 cells), miR-145 mimics induced EMT, whereas miR-145 inhibition suppressed EMT, and we also observed that miR-145 suppressed FGF10 expression. In vivo, we found that the exogenous delivery of an miR-145 expression plasmid both blocked FGF10 and intensified the EMT, whereas miR-145 inhibition promoted the expression of FGF10 and reversed the EMT. In conclusion, miR-145 promotes the EMT during the development of peritoneal fibrosis by suppressing FGF10 activity, suggesting that miR-145 represents a potential therapeutic target for managing peritoneal fibrosis.

Wu J ，Huang Q ，Li P ，Wang Y ，Zheng C ，Lei X ，Li S ，Gong W ，Yin B ，Luo C ，Xiao J ，Zhou W ，Xu Z ，Chen Y ，Peng F ，Long H ... -  《-》

MiR-200a negatively regulates TGF-β(1)-induced epithelial-mesenchymal transition of peritoneal mesothelial cells by targeting ZEB1/2 expression.

Guo R ，Hao G ，Bao Y ，Xiao J ，Zhan X ，Shi X ，Luo L ，Zhou J ，Chen Q ，Wei X ... -  《-》

MicroRNA-129-5p modulates epithelial-to-mesenchymal transition by targeting SIP1 and SOX4 during peritoneal dialysis.

Xiao L ，Zhou X ，Liu F ，Hu C ，Zhu X ，Luo Y ，Wang M ，Xu X ，Yang S ，Kanwar YS ，Sun L ... -  《-》