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Am J Physiol Renal Physiol 278: F110-F121, 2000;
0363-6127/00 $5.00
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Vol. 278, Issue 1, F110-F121, January 2000

Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats

Hirokazu Okada1, Kenshi Moriwaki1, Raghuram Kalluri2, Tsuneo Takenaka1, Hiroe Imai1, Shinichi Ban3, Motohide Takahama3, and Hiromichi Suzuki1

Departments of 1 Nephrology and 3 Pathology, Saitama Medical College, Saitama 350-04, Japan; and 2 Nephrology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215

In this study, we have shown that intravenously administered antisense oligodeoxynucleotide (ODN) was demonstrated to be taken up by tubular epithelium, after which it blocked mRNA expression of target genes in normal and nephritic rats. Therefore, we injected osteopontin (OPN) antisense ODN to Goodpasture syndrome (GPS) rats every second day between days 27 and 35, the time when renal OPN expression increased and interstitial monocyte infiltration was aggravated. In parallel to blockade of tubular OPN expression, this treatment significantly attenuated monocyte infiltration and preserved renal plasma flow in GPS rats at day 37, compared with sense ODN-treated and untreated GPS rats. No significant changes were observed in OPN mRNA level by RT-PCR and histopathology of the glomeruli after ODN treatment, which was compatible with an absence of differences in the urinary protein excretion rate. In conclusion, OPN expressed by tubular epithelium played a pivotal role in mediating peritubular monocyte infiltration consequent to glomerular disease.

antisense oligodeoxynucleotide; glomerular and interstitial histopathology; proteinuria; glomerular filtration rate; renal plasma flow


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