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Updated: Oct 3, 2026
Quantitative Real-Time PCR Evaluation of microRNA Expressions in Mouse Kidney with Unilateral Ureteral Obstruction
Published on: August 27, 2020
[Antisense oligonucleotide attenuates renal tubulointerstitial injury in mice with unilateral ureteral obstruction]
Objective:
To inhibit the expression of ICAM-1 mRNA with the mouse ICAM-1 phosphorothioate antisense oligodeoxynucleotide (ASON) and to investigate the role of ICAM-1 in the pathophysialogical process of renal injury in unilateral ureteral obstruction (UUO) animal model.
Methods:
After unilateral ureteral ligation, the mice were treated with ICAM-1 ASON, which was injected intravenously at the dosage of 1 mg/kg/day every other day for one week. Other mice treated with control oligonucleotide or normal saline solution only were taken as controls. The expression of ICAM-1 protein and the number of Mac-1 positive cells were measured by immunohistochemical staining. The pathological changes of the obstructed kidney in the mice were analyzed by PAS-staining. Total RNA renal tissue was extracted for the analysis of the ICAM-1 mRNA by methods of Northern blotting.
Results:
The expression of ICAM-1 protein and the number of Mac-1 positive cells were reduced markedly in the obstructed kidneys of the mice treated with the ICAM-1 ASON(110 +/- 14 [symbol: see text]/mm2 vs 270 +/- 13 [symbol: see text]/mm2). The results of Northern blotting also showed marked decrease of the expression of ICAM-1 mRNA in the kidney of the mice after treatment with ICAM-1 ASON. There were marked inflammatory cells infiltration in the tubulointerstitium, markedly dilated tubules, and extraceliular matrix accumulation in the obstructed kidneys on the 7th day after UUO operation. The treatment of ICAM-1 ASON can alleviate the lesions of the obstructed kidney except for the dilation of the tubules. There was no difference in the body weight, liver weight, spleen weight, the level of BUN and SCr, the level of GPT as well as the urine protein of the mice treated with ICAM-1 ASON, compared with those in control Oligodeoxynucleotide-treated and saline-treated mice.
Conclusions:
ICAM-1 is a very important factor in the pathogenesis of the UUO animal model. The mouse ICAM-1 ASON has therapeutic effects on the injury of the obstructed kidney without apparent side effects.
Insights
Antisense oligodeoxynucleotides targeting intercellular adhesion molecule-1 (ICAM-1 ASON) effectively reduced ICAM-1 expression and mitigated kidney injury in a mouse model of unilateral ureteral obstruction (UUO). This therapeutic approach shows promise for treating obstructive nephropathy.
Area of Science:
- Nephrology
- Molecular Biology
- Immunology
Context:
- Unilateral ureteral obstruction (UUO) is a common model for studying kidney injury.
- Intercellular Adhesion Molecule-1 (ICAM-1) plays a significant role in inflammatory processes and tissue damage.
- Understanding the role of ICAM-1 in UUO is crucial for developing targeted therapies.
Purpose:
- To investigate the therapeutic potential of inhibiting ICAM-1 expression using mouse ICAM-1 phosphorothioate antisense oligodeoxynucleotide (ASON).
- To elucidate the specific role of ICAM-1 in the pathophysiology of renal injury within the UUO animal model.
Summary:
- Mice with UUO were treated with ICAM-1 ASON, demonstrating a significant reduction in ICAM-1 protein and mRNA expression.
- Immunohistochemical analysis revealed decreased Mac-1 positive cell infiltration in ICAM-1 ASON-treated kidneys.
- Pathological examination showed that ICAM-1 ASON treatment alleviated inflammatory cell infiltration and extracellular matrix accumulation, though tubule dilation persisted.
Impact:
- ICAM-1 ASON effectively inhibits ICAM-1 expression, suggesting its critical involvement in UUO-induced kidney injury.
- The study highlights the therapeutic efficacy of ICAM-1 ASON in ameliorating renal damage in the UUO model.
- ICAM-1 ASON treatment demonstrated no significant adverse effects on body weight, organ weights, or key biochemical markers.
