PMID- 10620196
OWN - NLM
STAT- MEDLINE
DCOM- 20000308
LR  - 20061115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 57
IP  - 1
DP  - 2000 Jan
TI  - Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human 
      membranous nephropathy.
PG  - 147-58
AB  - Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human 
      membranous nephropathy. BACKGROUND: Proteinuria plays a central role in the 
      progression of glomerular disease, and there is growing evidence suggesting that 
      it may determine tubular cell activation with release of chemokines and 
      fibrogenic factors, leading to interstitial inflammatory reaction. However, most 
      studies on this subject have been performed in experimental models, and the 
      experience in human kidney biopsies has been scarce. We analyzed the tissue 
      sections of patients with idiopathic membranous nephropathy (IMN), a 
      noninflammatory glomerular disease that may follow a progressive disease with 
      heavy persistent proteinuria, interstitial cell infiltration, and decline of 
      renal function. METHODS: Paraffin-embedded biopsy specimens from 25 patients with 
      IMN (13 progressive and 12 nonprogressive) were retrospectively studied by 
      immunohistochemistry [monocyte chemoattractant protein-1 (MCP-1), regulated on 
      activation normal T-cell expressed and secreted chemokine (RANTES), osteopontin 
      (OPN), platelet-derived growth factor-BB (PD-GF-BB)] and in situ hybridization 
      [MCP-1, RANTES, PDGF-BB, transforming growth factor-beta1 (TGF-beta1)]. Moreover, 
      we studied the presence of myofibroblasts, which were identified by the 
      expression of alpha-smooth muscle actin (alpha-SMA), the monocytes/macrophages 
      (CD68-positive cells), and T-cell infiltration (CD4+ and CD8+ cells). All of the 
      patients were nephrotic and without treatment at time of the biopsy. RESULTS: A 
      strong up-regulation of MCP-1, RANTES, and OPN expression was observed, mainly in 
      tubular epithelial cells, with a significant major intensity in the progressive 
      IMN patients. A strong correlation between the mRNA expression and the 
      corresponding protein was noted. The presence of these chemokines and OPN was 
      associated with interstitial cell infiltration. TGF-beta and PDGF were also 
      up-regulated, mainly in tubular epithelial cells, with a stronger expression in 
      the progressive IMN, and an association with the presence of myofibroblasts was 
      found. CONCLUSIONS: Patients with severe proteinuria and progressive IMN have an 
      overexpression in tubular epithelial cells of the chemokines MCP-1, RANTES, and 
      OPN and the profibrogenic cytokines PDGF-BB and TGF-beta. Because this 
      up-regulation was associated with an interstitial accumulation of mononuclear 
      cells and an increase in myofibroblastic activity, it is suggested that those 
      mediators are potential predictors of progression in IMN. Finally, based on 
      experimental data and the findings of this article, we speculate that severe 
      proteinuria is the main factor responsible for the up-regulation of these factors 
      in tubular epithelial cells.
FAU - Mezzano, S A
AU  - Mezzano SA
AD  - Division of Nephrology, School of Medicine, Universidad Austral, Valdivia, Chile. 
      smezzano@uach.cl
FAU - Droguett, M A
AU  - Droguett MA
FAU - Burgos, M E
AU  - Burgos ME
FAU - Ardiles, L G
AU  - Ardiles LG
FAU - Aros, C A
AU  - Aros CA
FAU - Caorsi, I
AU  - Caorsi I
FAU - Egido, J
AU  - Egido J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Chemokines/*genetics
MH  - Cytokines/*genetics
MH  - Female
MH  - Fibroblasts/metabolism
MH  - Glomerulonephritis, Membranous/*metabolism/pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Kidney/metabolism
MH  - Macrophages/pathology
MH  - Male
MH  - Middle Aged
EDAT- 2000/01/05 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/01/05 09:00
PHST- 2000/01/05 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/01/05 09:00 [entrez]
AID - S0085-2538(15)46714-6 [pii]
AID - 10.1046/j.1523-1755.2000.00830.x [doi]
PST - ppublish
SO  - Kidney Int. 2000 Jan;57(1):147-58. doi: 10.1046/j.1523-1755.2000.00830.x.