Abstract |
TGF-β/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-β/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-β/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.
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Authors | Jian-Wen Yu, Wen-Juan Duan, Xiao-Ru Huang, Xiao-Ming Meng, Xue-Qing Yu, Hui-Yao Lan |
Journal | Laboratory investigation; a journal of technical methods and pathology
(Lab Invest)
Vol. 94
Issue 9
Pg. 978-90
(Sep 2014)
ISSN: 1530-0307 [Electronic] United States |
PMID | 25046436
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA Probes
- MIRN29 microRNA, mouse
- MicroRNAs
- Smad Proteins
- Sp1 Transcription Factor
- Transforming Growth Factor beta
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Topics |
- Animals
- Base Sequence
- Blotting, Western
- DNA Probes
- Male
- Mice
- Mice, Inbred C57BL
- MicroRNAs
(genetics, physiology)
- Models, Animal
- Peritoneal Dialysis
- Peritoneal Fibrosis
(prevention & control)
- Real-Time Polymerase Chain Reaction
- Signal Transduction
- Smad Proteins
(metabolism)
- Sp1 Transcription Factor
(metabolism)
- Transfection
- Transforming Growth Factor beta
(metabolism)
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