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Updated: Aug 15, 2026
A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction
Published on: December 20, 2014
Effects of ICAM-1 antisense oligonucleotide on the tubulointerstitium in mice with unilateral ureteral obstruction
Unlabelled:
Effects of ICAM-1 antisense oligonucleotide on the renal tubulointerstitium in mice with unilateral ureteral obstruction.
Background:
To extend our previous study of the therapy of the renal lesions of unilateral ureteral obstruction (UUO) in mice by an inhibitor of intercellular adhesion molecule-1 (ICAM-1), we investigated the blocking effects of ICAM-1 antisense oligonucleotides (ASONs) on the ICAM-1 expression in mouse kidney.
Methods:
First, ICAM-1 ASON was transducted into mouse renal tubular epithelial cells to investigate the effects of ICAM-1 ASON in vitro. Second, fluorescein isothiocyanate (FITC)-labeled ICAM-1 ASON was injected intravenously to determine the distribution of the ASON in vivo. Third, the expression of ICAM-1 in kidney and the changes of renal morphology were observed to investigate the therapeutic effects of ICAM-1 ASON on the UUO mice in vivo.
Results:
The expressions of ICAM-1 in the epithelial cells induced by interleukin-1beta were inhibited by ICAM-1 ASON at the dosages of 100 and 200 nmol/L. Twenty-four hours after an introvenous injection with FITC-labeled ICAM-1 ASON, the highest level of fluorescein was detected within the proximal tubules in mouse kidney. Results of immunohistology and Northern blot showed that the ICAM-1 expression was markedly reduced in the obstructed kidney after treatment with ICAM-1 ASON. The ASON also alleviated the infiltration of inflammatory cells and accumulation of the extracellular matrix in the tubulointerstitium of UUO mice without apparent side effects.
Conclusion:
Our data demonstrate that ICAM-1 ASON is taken up primarily by the proximal tubular cells of mouse kidney. ICAM-1 ASON can selectively inhibit the ICAM-1 expression of the renal tubular cells both in vitro and in vivo.
Insights
Intercellular adhesion molecule-1 (ICAM-1) antisense oligonucleotides (ASONS) effectively reduced ICAM-1 expression in mouse kidneys. This treatment alleviated inflammation and extracellular matrix accumulation in unilateral ureteral obstruction (UUO) models.
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Unilateral ureteral obstruction (UUO) in mice causes renal tubulointerstitial lesions.
- Intercellular adhesion molecule-1 (ICAM-1) plays a role in these renal lesions.
- Previous studies explored ICAM-1 inhibitors for UUO therapy.
Purpose of the Study:
- To investigate the therapeutic effects of ICAM-1 antisense oligonucleotides (ASONS) on renal tubulointerstitial damage in a mouse model of UUO.
- To assess the ability of ICAM-1 ASONs to inhibit ICAM-1 expression in the mouse kidney.
Main Methods:
- In vitro studies assessed ICAM-1 ASON effects on mouse renal tubular epithelial cells.
- In vivo studies tracked the distribution of fluorescein isothiocyanate (FITC)-labeled ICAM-1 ASON in mouse kidneys.
- Immunohistology and Northern blot analyzed ICAM-1 expression and renal morphology in UUO mice treated with ICAM-1 ASON.
Main Results:
- ICAM-1 ASON effectively inhibited ICAM-1 expression in renal tubular epithelial cells in vitro.
- FITC-labeled ICAM-1 ASON primarily localized to proximal tubules after intravenous injection.
- Treatment with ICAM-1 ASON significantly reduced ICAM-1 expression, inflammatory cell infiltration, and extracellular matrix accumulation in UUO mouse kidneys without apparent side effects.
Conclusions:
- ICAM-1 ASON is preferentially taken up by proximal tubular cells in the mouse kidney.
- ICAM-1 ASON demonstrates selective inhibition of ICAM-1 expression in renal tubular cells both in vitro and in vivo.
- ICAM-1 ASON shows therapeutic potential for mitigating renal tubulointerstitial damage in UUO by targeting ICAM-1.
