Theranostics 2015; 5(2):110-123. doi:10.7150/thno.9717 This issue Cite

Research Paper

Chitosan/siRNA Nanoparticles Targeting Cyclooxygenase Type 2 Attenuate Unilateral Ureteral Obstruction-induced Kidney Injury in Mice

Chuanxu Yang2*, Line Nilsson1*, Muhammad Umar Cheema1, Yan Wang1, Jørgen Frøkiær1, Shan Gao2✉, Jørgen Kjems2, Rikke Nørregaard1✉

1. Department of Clinical Medicine, Aarhus University, Denmark;
2. Interdisciplinary Nanoscience Center, Department of Molecular Biology and Genetics, Aarhus University, Denmark.
*Chuanxu Yang and Line Nilsson contributed equally to this study.

Citation:
Yang C, Nilsson L, Cheema MU, Wang Y, Frøkiær J, Gao S, Kjems J, Nørregaard R. Chitosan/siRNA Nanoparticles Targeting Cyclooxygenase Type 2 Attenuate Unilateral Ureteral Obstruction-induced Kidney Injury in Mice. Theranostics 2015; 5(2):110-123. doi:10.7150/thno.9717. https://www.thno.org/v05p0110.htm
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Abstract

Graphic abstract

Cyclooxygenase type 2 (COX-2) plays a predominant role in the progression of kidney injury in obstructive nephropathy. The aim of this study was to test the efficacy of chitosan/small interfering RNA (siRNA) nanoparticles to knockdown COX-2 specifically in macrophages to prevent kidney injury induced by unilateral ureteral obstruction (UUO). Using optical imaging techniques and confocal microscopy, we demonstrated that chitosan/siRNA nanoparticles accumulated in macrophages in the obstructed kidney. Consistent with the imaging data, the obstructed kidney contained a higher amount of siRNA and macrophages. Chitosan-formulated siRNA against COX-2 was evaluated on RAW macrophages demonstrating reduced COX-2 expression and activity after LPS stimulation. Injection of COX-2 chitosan/siRNA nanoparticles in mice subjected to three-day UUO diminished the UUO-induced COX-2 expression. Likewise, macrophages in the obstructed kidney had reduced COX-2 immunoreactivity, and histological examination showed lesser tubular damage in COX-2 siRNA-treated UUO mice. Parenchymal inflammation, assessed by tumor necrosis factor-alpha (TNF-α) and interleukin 6 mRNA expression, was attenuated by COX-2 siRNA. Furthermore, treatment with COX-2 siRNA reduced heme oxygenase-1 and cleaved caspase-3 in UUO mice, indicating lesser oxidative stress and apoptosis. Our results demonstrate a novel strategy to prevent UUO-induced kidney damage by using chitosan/siRNA nanoparticles to knockdown COX-2 specifically in macrophages.

Keywords: Cyclooxygenase type 2, siRNA, chitosan, unilateral ureteral obstruction, mice.


Citation styles

APA
Yang, C., Nilsson, L., Cheema, M.U., Wang, Y., Frøkiær, J., Gao, S., Kjems, J., Nørregaard, R. (2015). Chitosan/siRNA Nanoparticles Targeting Cyclooxygenase Type 2 Attenuate Unilateral Ureteral Obstruction-induced Kidney Injury in Mice. Theranostics, 5(2), 110-123. https://doi.org/10.7150/thno.9717.

ACS
Yang, C.; Nilsson, L.; Cheema, M.U.; Wang, Y.; Frøkiær, J.; Gao, S.; Kjems, J.; Nørregaard, R. Chitosan/siRNA Nanoparticles Targeting Cyclooxygenase Type 2 Attenuate Unilateral Ureteral Obstruction-induced Kidney Injury in Mice. Theranostics 2015, 5 (2), 110-123. DOI: 10.7150/thno.9717.

NLM
Yang C, Nilsson L, Cheema MU, Wang Y, Frøkiær J, Gao S, Kjems J, Nørregaard R. Chitosan/siRNA Nanoparticles Targeting Cyclooxygenase Type 2 Attenuate Unilateral Ureteral Obstruction-induced Kidney Injury in Mice. Theranostics 2015; 5(2):110-123. doi:10.7150/thno.9717. https://www.thno.org/v05p0110.htm

CSE
Yang C, Nilsson L, Cheema MU, Wang Y, Frøkiær J, Gao S, Kjems J, Nørregaard R. 2015. Chitosan/siRNA Nanoparticles Targeting Cyclooxygenase Type 2 Attenuate Unilateral Ureteral Obstruction-induced Kidney Injury in Mice. Theranostics. 5(2):110-123.

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