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  • Title: Inhibition of monocyte chemoattractant protein-1 expression in tubular epithelium attenuates tubulointerstitial alteration in rat Goodpasture syndrome.
    Author: Okada H, Moriwaki K, Kalluri R, Imai H, Ban S, Takahama M, Suzuki H.
    Journal: Kidney Int; 2000 Mar; 57(3):927-36. PubMed ID: 10720946.
    Abstract:
    BACKGROUND: To examine the role of monocyte chemoattractant protein-1 (MCP-1) expressed by tubular epithelium in tubulointerstitial alterations in situ, the level of MCP-1 mRNA in tubular epithelium was lowered selectively in the rat model of Goodpasture syndrome (GPS). METHODS: Intravenously administered antisense oligodeoxynucleotide (ODN) is taken up by renal tubular epithelium and has been found to block expression of target genes in rats. MCP-1 antisense ODN was injected into GPS rats every second day from days 27 to 35 after immunization (this represents the time when renal MCP-1 mRNA level was increased and interstitial mononuclear cell infiltration was aggravated). RESULTS: In addition to a reduction in the level of tubular MCP-1 mRNA, antisense ODN treatment attenuated monocyte infiltration significantly and preserved renal function in GPS rats. However, ODN injection did not affect glomerular MCP-1 expression and glomerular histopathology, and there were no significant changes in the urinary protein excretion rate. CONCLUSION: Our findings provide direct evidence that MCP-1, expressed by tubular epithelium, plays a pivotal role in mediating secondary tubulointerstitial alterations in the GPS model.
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