PMID- 15954901
OWN - NLM
STAT- MEDLINE
DCOM- 20050922
LR  - 20220317
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 68
IP  - 1
DP  - 2005 Jul
TI  - Kidneys with heavy proteinuria show fibrosis, inflammation, and oxidative stress, 
      but no tubular phenotypic change.
PG  - 121-32
AB  - BACKGROUND: Sustained proteinuria is a major factor leading to kidney fibrosis 
      and end-stage renal failure. Tubular epithelial cells are believed to play a 
      crucial role in this process by producing mediators leading to fibrosis and 
      inflammation. Congenital nephrotic syndrome of the Finnish type (NPHS1) is a 
      genetic disease caused by mutations in a podocyte protein nephrin, which leads to 
      constant heavy proteinuria from birth. In this work we studied the 
      tubulointerstitial changes that occur in NPHS1 kidneys during infancy. METHODS: 
      The pathologic lesions and expression of profibrotic and proinflammatory factors 
      in nephrectomized NPHS1 kidneys were studied by immunohistochemistry, Western 
      blotting, and cytokine antibody array. Oxidative stress in kidneys was assessed 
      by measurement of gluthatione redox state. RESULTS: The results indicated that 
      (1) severe tubulointerstitial lesions developed in NPHS1 kidneys during infancy; 
      (2) tubular epithelial cells did not show transition into myofibroblasts as 
      studied by the expression of vimentin, alpha-smooth muscle actin (alpha-SMA), 
      collagen, and matrix metalloproteinases 2 and 9 (MMP-2 and -9); (3) the most 
      abundant chemokines in NPHS1 tissue were neutrophil activating protein-2 (NAP-2), 
      macrophage inhibiting factor (MIF), and monocyte chemoattractant protein-1 
      (MCP-1); (4) monocyte/macrophage cells expressing CD14 antigen were the major 
      inflammatory cells invading the interstitium; (5) the arteries and arterioles 
      showed intimal hypertrophy, but the microvasculature in NPHS1 kidneys remained 
      quite normal; and (6) excessive oxidative stress was evident in NPHS1 kidneys. 
      CONCLUSION: Heavy proteinuria in NPHS1 kidneys was associated with interstitial 
      fibrosis, inflammation, and oxidative stress. The tubular epithelial cells, 
      however, were resistant to proteinuria and did not show epithelial-mesenchymal 
      transition.
FAU - Kuusniemi, Arvi-Matti
AU  - Kuusniemi AM
AD  - Hospital for Children and Adolescents and Biomedicum Helsinki, University of 
      Helsinki, Helsinki, Finland.
FAU - Lapatto, Risto
AU  - Lapatto R
FAU - Holmberg, Christer
AU  - Holmberg C
FAU - Karikoski, Riitta
AU  - Karikoski R
FAU - Rapola, Juhani
AU  - Rapola J
FAU - Jalanko, Hannu
AU  - Jalanko H
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)
RN  - 0 (Membrane Proteins)
RN  - 0 (nephrin)
SB  - IM
MH  - Capillaries/immunology/metabolism/pathology
MH  - Chemokines/metabolism
MH  - Child, Preschool
MH  - Cytokines/metabolism
MH  - Fibrosis
MH  - Humans
MH  - Infant
MH  - Kidney Tubules/immunology/metabolism/*pathology
MH  - Macrophages/metabolism/pathology
MH  - Membrane Proteins/genetics
MH  - Monocytes/metabolism/pathology
MH  - Nephritis/genetics/immunology/metabolism/*pathology
MH  - Nephrotic Syndrome/genetics/immunology/metabolism/*pathology
MH  - *Oxidative Stress
MH  - Phenotype
MH  - Proteinuria/genetics/immunology/metabolism/*pathology
EDAT- 2005/06/16 09:00
MHDA- 2005/09/24 09:00
CRDT- 2005/06/16 09:00
PHST- 2005/06/16 09:00 [pubmed]
PHST- 2005/09/24 09:00 [medline]
PHST- 2005/06/16 09:00 [entrez]
AID - S0085-2538(15)50819-3 [pii]
AID - 10.1111/j.1523-1755.2005.00386.x [doi]
PST - ppublish
SO  - Kidney Int. 2005 Jul;68(1):121-32. doi: 10.1111/j.1523-1755.2005.00386.x.