Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats.
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.
Okada
H
H
Department of Nephrology, Saitama Medical College, Saitama 350-04, Japan.
Moriwaki
K
K
Kalluri
R
R
Takenaka
T
T
Imai
H
H
Ban
S
S
Takahama
M
M
Suzuki
H
H
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D053495:Osteopontin; D011507:Proteinuria / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*
D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin