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Published on: June 27, 2017
MicroRNA-29b inhibits peritoneal fibrosis in a mouse model of peritoneal dialysis
Jian-Wen Yu1, Wen-Juan Duan1, Xiao-Ru Huang2
11] Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China [2] Li Ka Shing Institute of Health Sciences and Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
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.
Insights
MicroRNA-29b (miR-29b) shows therapeutic potential against peritoneal fibrosis in peritoneal dialysis (PD) patients. This study demonstrates miR-29b can prevent and halt fibrosis progression, offering a novel treatment strategy for PD-related complications.
Area of Science:
- Nephrology
- Molecular Biology
- Biomedical Engineering
Background:
- Peritoneal fibrosis is a significant complication of peritoneal dialysis (PD).
- TGF-β/Smad3 signaling is a key pathway in peritoneal fibrosis.
- MicroRNA-29 (miR-29) family members are known inhibitors of TGF-β/Smad3 signaling.
Purpose of the Study:
- To investigate the therapeutic efficacy of miR-29b in a mouse model of PD-induced peritoneal fibrosis.
- To explore the underlying mechanism of miR-29b's action on peritoneal fibrosis.
Main Methods:
- A mouse model of PD was established using daily infusion of 4.25% dextrose PD fluid.
- miR-29b-expressing plasmid was delivered via ultrasound-microbubble system before and after PD induction.
- Peritoneal function, fibrosis markers (including epithelial-mesenchymal transition - EMT), and miR-29b levels were assessed.
Main Results:
- PD mice developed peritoneal fibrosis and dysfunction, correlated with reduced miR-29b levels.
- Pre-emptive miR-29b treatment protected against fibrosis and peritoneal dysfunction.
- Delayed miR-29b treatment halted established fibrosis progression.
- miR-29b appears to inhibit peritoneal fibrosis by blocking the Sp1-TGF-β/Smad3 pathway.
Conclusions:
- miR-29b demonstrates protective and therapeutic effects against PD-associated peritoneal fibrosis.
- miR-29b may represent a novel therapeutic agent for treating peritoneal fibrosis in PD patients.
