Suppression of stent-induced tissue hyperplasia in rats by using small interfering RNA to target matrix metalloproteinase-9

Abstract

Background and study aims: We evaluated the efficacy of small interfering RNA (siRNA) in targeting matrix metalloproteinase (MMP-9) to suppress stent-induced tissue hyperplasia in a rat esophageal model. Methods: The silencing effect of the candidate siRNA (termed (MMP-9 siRNA) was evaluated in 9L rat glial cells. Four groups of rats (n = 10, each group) were used: Eso-S, stent insertion only, comparison; Eso-R, stent insertion plus treatment with MMP-9 siRNA complexed with Chol-R9 for delivery, experimental; Eso-P, stent insertion plus treatment with pCMV-luc complexed with Chol-R9, for confirmation of Chol-R9 delivery effect; and Eso-N, no stent insertion and no treatment, controls. All rats were sacrificed at 3 weeks. The therapeutic efficacy of the MMP-9 siRNA/Chol-R9 complex was assessed. Results: The most potent MMP-9 siRNA was selected. Compared with the Eso-S group, the EsoR group showed significantly less tissue hyperplasia with a lower percentage of granulation tissue and smaller granulation tissue area, and also significantly lower MMP-9 level. Conclusions: MMP-9 siRNA/Chol-R9 is effective for inhibiting stent-induced tissue hyperplasia in a rat esophageal model.