Document Detail

Extracellular signal-regulated kinase-dependent interstitial macrophage proliferation in the obstructed mouse kidney.
MedLine Citation:
PMID:  18331439     Owner:  NLM     Status:  MEDLINE    
AIM: A number of growth factors have been shown to induce proliferation of renal cell types in animal models of kidney disease. In vitro studies suggest that many such growth factors induce renal cell proliferation through the extracellular signal-regulated kinase (ERK) pathway. The aim of this study was to determine the functional role of ERK signalling in cell proliferation in the obstructed kidney. METHODS: Unilateral ureteric obstruction was induced in C57BL/6J mice which then received an ERK inhibitor drug (U0126 100 mg/kg t.i.d.), vehicle (DMSO) or no treatment, starting at day 2 after unilateral ureteric obstruction surgery and continuing until animals were killed on day 5. Cell proliferation was assessed by uptake of bromodeoxyuridine (BrdU). RESULTS: In normal mice, phosphorylation (activation) of ERK (p-ERK) was restricted to collecting ducts. Western blotting identified a marked increase in p-ERK in the obstructed kidney in the no-treatment and vehicle-treated groups. Immunostaining showed strong p-ERK staining in many tubules and in interstitial cells. U0126 treatment inhibited ERK phosphorylation as assessed by western blot and immunostaining. The number of BrdU+ cortical tubular cells was reduced by vehicle treatment but was not further changed by U0126 treatment. In contrast, interstitial cell proliferation in the obstructed kidney was unaltered by vehicle treatment, but this was significantly inhibited by U0126. This was associated with a reduction in interstitial macrophage accumulation, but no effect was seen upon interstitial accumulation of alpha-SMA+ myofibroblasts. Renal fibrosis, as assessed by collagen deposition, was unaffected by U0126 or vehicle treatment. CONCLUSION: These studies show that accumulation of interstitial macrophages in the obstructed kidney is, in part, dependent upon the ERK signalling pathway.
Yingjie Han; Takao Masaki; Lynette A Hurst; Yohei Ikezumi; James M Trzaskos; Robert C Atkins; David J Nikolic-Paterson
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Publication Detail:
Type:  Journal Article     Date:  2008-03-05
Journal Detail:
Title:  Nephrology (Carlton, Vic.)     Volume:  13     ISSN:  1440-1797     ISO Abbreviation:  Nephrology (Carlton)     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-10     Completed Date:  2009-02-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9615568     Medline TA:  Nephrology (Carlton)     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  411-8     Citation Subset:  IM    
Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, Australia.
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MeSH Terms
Butadienes / administration & dosage,  pharmacology
Cell Proliferation / drug effects
Enzyme Inhibitors / administration & dosage,  pharmacology
Kidney Diseases / enzymology*
Macrophages / drug effects
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase Kinases / metabolism*
Nitriles / administration & dosage,  pharmacology
Signal Transduction*
Ureteral Obstruction / surgery
Reg. No./Substance:
0/Butadienes; 0/Enzyme Inhibitors; 0/Nitriles; 0/U 0126; EC Protein Kinase Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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