Effects of ICAM-1 antisense oligonucleotide on the tubulointerstitium in mice with unilateral ureteral obstruction.
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.


CONCLUSIONS
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.
Cheng
Q L
QL
Division of Nephrology, General Hospital of Chinese PLA, Beijing, China
Chen
X M
XM
Li
F
F
Lin
H L
HL
Ye
Y Z
YZ
Fu
B
B
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D014517:Ureteral Obstruction
D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D018799:Intercellular Adhesion Molecule-1