Abstract | BACKGROUND/AIM: METHODS: The HSP47 siRNA was injected once via the ureter at the time of UUO preparation. We also applied a new gene delivery system for siRNA using cationized gelatin microspheres. The kidneys were harvested 7 and 14 days after UUO. The HSP47 and type I, III, and IV collagen expression levels were analyzed by immunohistochemistry and Western blotting. RESULTS: Seven days after UUO, the expression levels of HSP47 and type I, III, and IV collagens were markedly upregulated in obstructed kidneys or green fluorescent protein siRNA treated obstructed kidneys. HSP47 siRNA injection significantly reduced the protein expression levels and significantly diminished the accompanying interstitial fibrosis. Moreover, cationized gelatin microspheres as a delivery system enhanced and lengthened the antifibrotic effect of HSP47 siRNA. CONCLUSIONS: Our results indicate that HSP47 is a candidate target for the prevention of tubulointerstitial fibrosis and that selective blockade of the HSP47 expression by using siRNA could be a potentially useful therapeutic approach for patients with renal disease.
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Authors | Zhiyin Xia, Katsushige Abe, Akira Furusu, Masanobu Miyazaki, Yoko Obata, Yasuhiko Tabata, Takehiko Koji, Shigeru Kohno |
Journal | American journal of nephrology
(Am J Nephrol)
Vol. 28
Issue 1
Pg. 34-46
( 2008)
ISSN: 1421-9670 [Electronic] Switzerland |
PMID | 17890856
(Publication Type: Journal Article)
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Copyright | (c) 2007 S. Karger AG, Basel. |
Chemical References |
- Collagen Type I
- Collagen Type III
- Collagen Type IV
- HSP47 Heat-Shock Proteins
- RNA, Small Interfering
- Serpinh1 protein, mouse
- Green Fluorescent Proteins
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Topics |
- Animals
- Collagen Type I
(genetics)
- Collagen Type III
(genetics)
- Collagen Type IV
(genetics)
- Disease Models, Animal
- Fibrosis
- Genetic Therapy
(methods)
- Green Fluorescent Proteins
(genetics)
- HSP47 Heat-Shock Proteins
(genetics)
- Macrophages
(pathology)
- Male
- Mice
- Mice, Inbred ICR
- Microinjections
- Nephritis, Interstitial
(pathology, physiopathology, therapy)
- RNA, Small Interfering
(pharmacology)
- Ureteral Obstruction
(pathology, physiopathology, therapy)
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