First Author | Yu JW | Year | 2014 |
Journal | Lab Invest | Volume | 94 |
Issue | 9 | Pages | 978-90 |
PubMed ID | 25046436 | Mgi Jnum | J:214226 |
Mgi Id | MGI:5588598 | Doi | 10.1038/labinvest.2014.91 |
Citation | Yu JW, et al. (2014) MicroRNA-29b inhibits peritoneal fibrosis in a mouse model of peritoneal dialysis. Lab Invest 94(9):978-90 |
abstractText | TGF-beta/Smad3 signaling plays a pivotal role in the pathogenesis of peritoneal fibrosis associated with peritoneal dialysis (PD). MicroRNA-29 (miR-29) is known as a potent downstream inhibitor of TGF-beta/Smad3 in renal fibrosis. In this study, we examined the therapeutic potential for miR-29b on PD-related peritoneal fibrosis in a mouse model of PD induced by daily infusion of 4.25% dextrose-containing PD fluid (PDF). MiR-29b-expressing plasmid was delivered into the peritoneum via an ultrasound-microbubble-mediated system before and at day 14 after PDF. We found that mice on PD developed peritoneal fibrosis with impaired peritoneal function, which was associated with a loss of miR-29b. In contrast, overexpression of miR-29b before the PDF infusion showed a protective effect on peritoneal fibrosis including EMT and prevented peritoneal dysfunction. Moreover, delayed miR-29b treatment until peritoneal fibrosis was established at day 14 also halted the progression of peritoneal fibrosis at day 28. Further studies identified that blockade of the Sp1-TGF-beta/Smad3 pathway may be a mechanism by which miR-29b inhibited peritoneal fibrosis. In conclusion, treatment with miR-29b may represent a novel and effective therapy for PD-associated peritoneal fibrosis. |