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Bioreducible Polymer–delivered siRNA Targeting MMP-9: Suppression of Granulation Tissue Formation after Bare Metallic Stent Placement in a Rat Urethral Model

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Title
Bioreducible Polymer–delivered siRNA Targeting MMP-9: Suppression of Granulation Tissue Formation after Bare Metallic Stent Placement in a Rat Urethral Model
Author(s)
Jung-Hoon Park; Jin Hyoung Kim; Eun-Young Kim; Jinoo Kim; Ho-Young Song; Won Jong Kim; Duhwan Lee; Jihong Park; Soohwan Kim
Publication Date
2014-04
Journal
RADIOLOGY, v.271, no.1, pp.87 - 95
Publisher
RADIOLOGICAL SOC 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–SSICG), 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://pr.ibs.re.kr/handle/8788114/792
ISSN
0033-8419
Appears in Collections:
Center for Self-assembly and Complexity(복잡계 자기조립 연구단) > Journal Papers (저널논문)
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