PMID- 12814691
OWN - NLM
STAT- MEDLINE
DCOM- 20031023
LR  - 20190827
IS  - 0302-2838 (Print)
IS  - 0302-2838 (Linking)
VI  - 44
IP  - 1
DP  - 2003 Jul
TI  - Epidermal growth factor and monocyte chemotactic peptide-1 expression in reflux 
      nephropathy.
PG  - 144-9
AB  - OBJECTIVES: Reflux nephropathy (RN) is recognised as a major cause of end stage 
      renal failure in children and young adults. The histological findings of RN are 
      tubular atrophy and interstitial monocyte infiltration. Epidermal growth factor 
      (EGF) produced by tubular cells playing a pivotal role in the modulation of 
      tubular cell growth, while monocyte chemotactic peptide-1 (MCP-1) is a powerful 
      and specific chemotactic and activating factor for monocytes. It has been 
      suggested that the modulation of local EGF production is directly involved in the 
      pathogenesis of tubular damage. We designed this study to investigate the 
      expression of EGF and MCP-1 in severe reflux nephropathy in order to further 
      understand the pathogenesis of reflux nephropathy. METHODS: The kidney specimens 
      from 12 children with severe reflux nephropathy were obtained at the time of 
      nephrectomy. Control material included normal kidney specimens obtained from 
      three adult patients during partial nephrectomy for an incidentaloma. 
      Single-label immunofluorescence histochemistry was carried out using polyclonal 
      antibodies to EGF and MCP-1 employing laser scanning confocal microscopy. EGF and 
      MCP-1 gene expression were evaluated by in situ hybridization (ISH). TUNEL method 
      was utilized to assess tubular apoptosis. RESULTS: In the normal kidney there was 
      strong EGF immunoreactivity in the proximal tubules compared to the reflux 
      nephropathy where there was lack of immunoreactivity in the proximal tubules. 
      Normal kidney demonstrated lack of MCP-1 immunoreactivity, whereas reflux 
      nephropathy kidney showed strong MCP-1 immunoreactivity in the proximal tubules 
      and tubulointerstitial space. In the normal kidney there was marked EGF mRNA 
      expression in the proximal tubules whereas EGF mRNA expression was undetectable 
      in reflux nephropathy kidney. MCP-1 mRNA expression was undetectable in normal 
      kidney, whereas there was strong MCP-1 mRNA expression at the tubulointerstitial 
      level in reflux nephropathy kidney. Decreased EGF expression and increased MCP-1 
      expression at the tubulointerstitial levels in reflux nephropathy strongly 
      correlated with severity of apoptosis in reflux nephropathy compared with 
      controls. CONCLUSIONS: Our data suggests that the downregulation of EGF with 
      simultaneous upregulation of MCP-1 may be involved in the pathogenesis of 
      tubulointerstitial damage in reflux nephropathy.
FAU - Chertin, Boris
AU  - Chertin B
AD  - Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, 
      University College Dublin, Dublin 12, Ireland.
FAU - Farkas, Amicur
AU  - Farkas A
FAU - Puri, Prem
AU  - Puri P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Switzerland
TA  - Eur Urol
JT  - European urology
JID - 7512719
RN  - 0 (Biomarkers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Adolescent
MH  - Biomarkers/analysis
MH  - Case-Control Studies
MH  - Chemokine CCL2/analysis/*metabolism
MH  - Child
MH  - Child, Preschool
MH  - Culture Techniques
MH  - Down-Regulation
MH  - Epidermal Growth Factor/analysis/*metabolism
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - In Situ Nick-End Labeling
MH  - Infant
MH  - Kidney Diseases/*etiology/*pathology/surgery
MH  - Male
MH  - Nephrectomy
MH  - Probability
MH  - Prognosis
MH  - RNA, Messenger/analysis
MH  - Sensitivity and Specificity
MH  - Severity of Illness Index
MH  - Statistics, Nonparametric
MH  - Up-Regulation
MH  - Vesico-Ureteral Reflux/*complications
EDAT- 2003/06/20 05:00
MHDA- 2003/10/24 05:00
CRDT- 2003/06/20 05:00
PHST- 2003/06/20 05:00 [pubmed]
PHST- 2003/10/24 05:00 [medline]
PHST- 2003/06/20 05:00 [entrez]
AID - S0302283803001908 [pii]
AID - 10.1016/s0302-2838(03)00190-8 [doi]
PST - ppublish
SO  - Eur Urol. 2003 Jul;44(1):144-9. doi: 10.1016/s0302-2838(03)00190-8.