rAAV9-mediated supplementation of miR-29b improve angiotensin-II induced renal fibrosis in mice.
Mol Med
; 27(1): 89, 2021 08 18.
Article
em En
| MEDLINE
| ID: mdl-34407760
BACKGROUND: Renin-angiotensin-aldosterone system activation is the critical factor in renal remodeling and dysfunction. Our previous study suggested that miR-29b may attenuate AngII-induced renal intestinal fibrosis in vitro. In the present study, we aimed to determine whether recombinant rAAV9-mediated miR-29b delivery protects against AngII-induced renal fibrosis and dysfunction. METHOD: Mice were treated with AngII via osmotic mini-pumps, or phosphate-buffered saline. rAAV9 vectors were produced using the rBac-based system in SF9 cells. rAAV9-miR-29b or rAAV9-control-miR was injected into the kidneys of mice subjected to the model of AngII infusion. The role of miR-29b in renal fibrosis was assessed using quantitative polymerase chain reaction, western blot, and histology. RESULTS: In AngII-induced fibrotic kidney tissue, miR-29b expression was downregulated. rAAV9-miR-29b delivery significantly reversed renal injury as indicated by decreased serum creatinine and injury related gene expression in AngII-infused mice. Regarding organ remodeling, tubulointerstitial fibrosis and deposition of extracellular matrix components such as collagen type I and type III were significantly decreased in renal tissue from mice delivered rAAV9-miR-29b. CONCLUSION: Our results demonstrate great potential for use of rAAV9 as an applicable vector for delivery of miR-29b as an antifibrogenic factor for treatment of tubulointerstitial fibrosis-induced renal injury.
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Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Transdução Genética
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Angiotensina II
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Dependovirus
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MicroRNAs
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Vetores Genéticos
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Nefropatias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article