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

In this study, we have shown that intravenously administered antisense olig odeoxynucleotide (ODN) was demonstrated to be taken up by tubular epitheliu m, after which it blocked mRNA expression of target genes in normal and nep hritic rats. Therefore, we injected osteopontin (OPN) antisense ODN to Good pasture syndrome (GPS) rats every second day between days 27 and 35, the ti me when renal OPN expression increased and interstitial monocyte infiltrati on was aggravated. In parallel to blockade of tubular OPN expression, this treatment significantly attenuated monocyte infiltration and preserved rena l plasma flow in GPS rats at day 37, compared with sense ODN-treated and un treated 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 r ole in mediating peritubular monocyte infiltration consequent to glomerular disease.