PMID- 10720946 OWN - NLM STAT- MEDLINE DCOM- 20000518 LR - 20061115 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 57 IP - 3 DP - 2000 Mar TI - Inhibition of monocyte chemoattractant protein-1 expression in tubular epithelium attenuates tubulointerstitial alteration in rat Goodpasture syndrome. PG - 927-36 AB - 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. FAU - Okada, H AU - Okada H AD - Department of Nephrology, Saitama Medical College, Japan. FAU - Moriwaki, K AU - Moriwaki K FAU - Kalluri, R AU - Kalluri R FAU - Imai, H AU - Imai H FAU - Ban, S AU - Ban S FAU - Takahama, M AU - Takahama M FAU - Suzuki, H AU - Suzuki H LA - eng PT - Journal Article PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Chemokine CCL2) RN - 0 (Oligonucleotides, Antisense) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Anti-Glomerular Basement Membrane Disease/*metabolism/pathology/physiopathology MH - Chemokine CCL2/*antagonists & inhibitors/genetics/metabolism MH - Epithelium/metabolism MH - Kidney/metabolism/pathology/physiopathology MH - Kidney Tubules/*metabolism MH - Male MH - Oligonucleotides, Antisense/pharmacology MH - RNA, Messenger/antagonists & inhibitors/metabolism MH - Rats MH - Rats, Wistar MH - Tissue Distribution EDAT- 2000/03/18 09:00 MHDA- 2000/05/20 09:00 CRDT- 2000/03/18 09:00 PHST- 2000/03/18 09:00 [pubmed] PHST- 2000/05/20 09:00 [medline] PHST- 2000/03/18 09:00 [entrez] AID - S0085-2538(15)46825-5 [pii] AID - 10.1046/j.1523-1755.2000.00909.x [doi] PST - ppublish SO - Kidney Int. 2000 Mar;57(3):927-36. doi: 10.1046/j.1523-1755.2000.00909.x.