Bioreducible Polymer-delivered siRNA Targeting MMP-9: Suppression of Granulation Tissue Formation after Bare Metallic Stent Placement in a Rat Urethral Model
SCIE
SCOPUS
- Title
- Bioreducible Polymer-delivered siRNA Targeting MMP-9: Suppression of Granulation Tissue Formation after Bare Metallic Stent Placement in a Rat Urethral Model
- Authors
- Park, JH; Kim, JH; Kim, EY; Kim, J; Song, HY; Kim, WJ; Lee, D; Park, J; Kim, S
- Date Issued
- 2014-04
- Publisher
- Radiological Society of North America
- Abstract
- To evaluate the effectiveness of small interfering RNA (siRNA) targeting matrix metalloproteinase 9 (MMP-9) in suppressing granulation tissue formation caused by bare metallic stent placement in a rat urethral model. All experiments were approved by the committee of animal research. In 20 Sprague-Dawley male rats (weight range, 300-350 g), a self-expanding metallic bare stent was inserted in the urethra with fluoroscopic guidance. One group of 10 rats (group A) was treated with MMP-9 siRNA/bioreducible branched polyethylenimine-disulfide cross-linked-indocyanine green (bioreducible BPEI-SS-ICG), while the other group of 10 rats (group B) received control siRNA/bioreducible BPEI-SS-ICG treatment. All rats were sacrificed at 4 weeks. The therapeutic effectiveness of the MMP-9 siRNA/bioreducible BPEI-SS-ICG complex was assessed by comparing the two results of retrograde urethrography, histologic examination, and quantification of MMP-9 by using zymography and Western blot analysis between the two groups. The Mann-Whitney U test was used to evaluate differences. Stent placement was successful in all rats without a single case of migration at follow-up. Retrograde urethrography performed 4 weeks after stent placement demonstrated significantly larger luminal diameters of the urethra within the stents in group A compared with those in group B (P = .011). Histologic analysis revealed that the mean percentage of granulation tissue area (P < .001), mean number of epithelial layers (P < .001), and mean thickness of submucosal fibrosis (P < .001) were significantly decreased in group A compared with group B. Meanwhile, the mean density of inflammatory cell infiltration did not significantly differ between the two groups (P = .184). Quantitative analysis disclosed MMP-9 levels to be lower in group A relative to group B, indicating positive inhibition of MMP-9 by MMP-9 siRNA/bioreducible BPEI-SS-ICG. MMP-9 siRNA/bioreducible BPEI-SS-ICG is effective for inhibiting granulation tissue formation after bare metallic stent placement in a rat urethral model.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/13865
- DOI
- 10.1148/RADIOL.13130980
- ISSN
- 0033-8419
- Article Type
- Article
- Citation
- Radiology, vol. 271, no. 1, page. 87 - 95, 2014-04
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