RGD Reference Report - siRNA-based therapy ameliorates glomerulonephritis. - Rat Genome Database

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siRNA-based therapy ameliorates glomerulonephritis.

Authors: Shimizu, H  Hori, Y  Kaname, S  Yamada, K  Nishiyama, N  Matsumoto, S  Miyata, K  Oba, M  Yamada, A  Kataoka, K  Fujita, T 
Citation: Shimizu H, etal., J Am Soc Nephrol. 2010 Apr;21(4):622-33. doi: 10.1681/ASN.2009030295. Epub 2010 Mar 4.
RGD ID: 7243972
Pubmed: PMID:20203158   (View Abstract at PubMed)
PMCID: PMC2844303   (View Article at PubMed Central)
DOI: DOI:10.1681/ASN.2009030295   (Journal Full-text)

RNA interference by short interfering RNAs (siRNAs) holds promise as a therapeutic strategy, but use of siRNAs in vivo remains limited. Here, we developed a system to target delivery of siRNAs to glomeruli via poly(ethylene glycol)-poly(l-lysine)-based vehicles. The siRNA/nanocarrier complex was approximately 10 to 20 nm in diameter, a size that would allow it to move across the fenestrated endothelium to access to the mesangium. After intraperitoneal injection of fluorescence-labeled siRNA/nanocarrier complexes, we detected siRNAs in the blood circulation for a prolonged time. Repeated intraperitoneal administration of a mitogen-activated protein kinase 1 (MAPK1) siRNA/nanocarrier complex suppressed glomerular MAPK1 mRNA and protein expression in a mouse model of glomerulonephritis; this improved kidney function, reduced proteinuria, and ameliorated glomerular sclerosis. Furthermore, this therapy reduced the expression of the profibrotic markers TGF-beta1, plasminogen activator inhibitor-1, and fibronectin. In conclusion, we successfully silenced intraglomerular genes with siRNA using nanocarriers. This technique could aid the investigation of molecular mechanisms of renal disease and has potential as a molecular therapy of glomerular diseases.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MAPK1Humanglomerulonephritis  ISOMapk1 (Mus musculus) RGD 
Mapk1Ratglomerulonephritis  ISOMapk1 (Mus musculus) RGD 
Mapk1Mouseglomerulonephritis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mapk1  (mitogen activated protein kinase 1)

Genes (Mus musculus)
Mapk1  (mitogen-activated protein kinase 1)

Genes (Homo sapiens)
MAPK1  (mitogen-activated protein kinase 1)


Additional Information