Abstract
BackgroundRenin–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.MethodMice 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.ResultsIn 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.ConclusionOur 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.
Highlights
Renin–angiotensin–aldosterone system activation is the critical factor in renal remodeling and dys‐ function
We found that Med (2021) 27:89MicroRNAs (miRs)-29b was downregulated in the kidneys of spontaneously hypertensive rats and AngII-stimulated NRK52E cells, suggesting it may protect against fibrosis by suppressing deposition of extracellular matrix (ECM) components and preventing the Epithelial-mesenchymal transition (EMT) (Pan et al 2014)
RAAV9GFP particles were injected into mouse kidneys, and GFP expression was measured to evaluate the efficiency of Recombinant adeno-associated virus serotype 9 (rAAV9) gene transduction
Summary
Renin–angiotensin–aldosterone system activation is the critical factor in renal remodeling and dys‐ function. Our previous study suggested that miR-29b may attenuate AngII-induced renal intestinal fibrosis in vitro. We aimed to determine whether recombinant rAAV9-mediated miR-29b delivery protects against AngII-induced renal fibrosis and dysfunction. Renal interstitial fibrosis is a primary feature of numerous chronic kidney disorders, and it contributes to end-stage renal failure. Multiple extracellular matrix (ECM) components, collagen type I and III, play crucial roles in interstitial fibrosis (Zeisberg and Neilson 2010). MicroRNAs (miRs) regulate gene expression by promoting mRNA degradation or translation inhibition. Emerging evidence shows that miRs play pathological roles in kidney diseases. Many studies demonstrated that miRs are either affected by RAAS inhibitors or target RAAS effectors (DuPont et al 2016). MiRs may represent novel therapeutic targets for RAAS overactivation-induced kidney remodeling
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