title: MicroRNA-29b inhibits peritoneal fibrosis in a mouse model of peritoneal dialysis.
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.
authors.affiliation: 1] 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.
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Yu
authors.affiliation: 1] 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.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Duan
authors.affiliation: 1] Li Ka Shing Institute of Health Sciences and Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, China [2] Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Huang
authors.affiliation: Li Ka Shing Institute of Health Sciences and Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Meng
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Yu
authors.affiliation: 1] Li Ka Shing Institute of Health Sciences and Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, China [2] Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
authors.forename: Hui-Yao
authors.initials: HY
authors.lastname: Lan
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D015342:DNA Probes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D023421:Models, Animal; D010530:Peritoneal Dialysis; D056627:Peritoneal Fibrosis / Q000517:prevention & control*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015342:DNA Probes; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D051785:Smad Proteins; D016329:Sp1 Transcription Factor; D016212:Transforming Growth Factor beta