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10.1038/labinvest.2015.57

http://scihub22266oqcxt.onion/10.1038/labinvest.2015.57
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C4863710!4863710!25961171
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suck abstract from ncbi


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pmid25961171      Lab+Invest 2015 ; 95 (7): 817-32
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  • MicroRNA-129-5p modulates epithelial-to-mesenchymal transition by targeting SIP1 and SOX4 during peritoneal dialysis #MMPMID25961171
  • Xiao L; Zhou X; Liu F; Hu C; Zhu X; Luo Y; Wang M; Xu X; Yang S; Kanwar YS; Sun L
  • Lab Invest 2015[Jul]; 95 (7): 817-32 PMID25961171show ga
  • Peritoneal dialysis (PD) is the most readily feasible home-dialysis method for renal replacement therapy. However, repeated use of PD can lead to induction of mesothelial/epithelial?mesenchymal transition (MMT/EMT) and fibrosis, eventually leading to ultrafiltration failure and discontinuation of PD. MicroRNA-129-5p (miR-129-5p) is believed to be a potent downstream inhibitor of TGF-?1 in renal fibrosis, but the effect of miR-129-5p on MMT/EMT relevant to PD is unknown. In this study, as determined by microRNA array analysis and confirmed by northern blot analysis and real-time PCR, we demonstrate that miRNA-129-5p is decreased in mesothelial cells isolated from effluent of patients having PD for more than 6 months extending to several years compared with those who have undergone PD for less than 6 months. The decreased expression of miR-129-5p was accompanied with alterations in EMT-related genes and the expression of respective proteins in vivo. In addition, in in vitro studies we noted that the expression of E-cadherin and claudin-1 were significantly reduced with increased cell migration in HMrSV5, a human peritoneal mesothelial cell line (HPMC), treated with TGF-?1, whereas expression of vimentin, fibronectin and transcription factors SIP1 and SOX4 increased significantly, as assessed by real-time PCR, western blot analysis and immunofluorescence microscopy. Furthermore, alteration in EMT-related genes and proteins were reversed by overexpression of miR-129-5p. No effect was observed in cells treated with miR-negative control. Meanwhile, inhibition of SIP1 and SOX4 with their respective siRNA also could decrease the expression of EMT-related genes and protein levels in HPMCs induced with TGF-?1. Finally, we demonstrate that SIP1 can inhibit the promoter activity of E-cadherin while enhancing the promoter activity of vimentin. We also observed that miR-129-5p could directly target the 3?UTR of SIP1 and SOX4 genes, and repressed their post-transcriptional activities. These data suggest that there is a novel TGF-?1/miR-129-5p/SIP-1 or SOX4 pathway that has a significant role in MMT and fibrosis in the setting of PD.
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