PMID- 17124284
OWN - NLM
STAT- MEDLINE
DCOM- 20070709
LR  - 20220408
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 22
IP  - 2
DP  - 2007 Feb
TI  - Possible mechanisms explaining the tendency towards interstitial fibrosis in 
      aristolochic acid-induced acute tubular necrosis.
PG  - 445-56
AB  - BACKGROUND: We explored possible mechanisms responsible for the inability of 
      plerosis and the tendency towards fibrosis in aristolochic acid-induced acute 
      tubular necrosis (AA-ATN). METHODS: Renal biopsy tissues from eight AA-ATN cases 
      were examined. Tubulointerstitial injury was semiquantitatively assessed. 
      Immunohistochemical steptavidin-peroxide (SP) methods were used to determine the 
      expressions of proliferating cell nuclear antigen (PCNA), epidermal growth factor 
      (EGF), alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta(1) 
      (TGF-beta(1)), connecting tissue growth factor (CTGF), fibronectin (FN), collagen 
      III (Col-III), collagen IV (Col-IV), factor VIII-related antigen (VIII-Ag) and 
      vascular endothelial growth factor (VEGF). Ultramicrostructure of endothelial 
      cells and basement membrane of peritubular capillaries (PTC) and glomerular 
      capillaries was detected by electron microscopy. These data were compared with 
      that of 9 cases of antibiotic-induced ATN (a-ATN) and 10 cases of minor 
      mesangioproliferative non-IgA glomerulonephritis, which served as a control 
      group. RESULTS: In AA-ATN, almost no renal tubular epithelial cells (RTEC) were 
      PCNA-positive (0.01 +/- 0.02%), and EGF expression was considerably decreased 
      (9.55 +/- 7.22%). This was in contrast with the highly active tubular 
      proliferation (PCNA-positive RTEC 47.25 +/- 19.33%, P < 0.05) and increased EGF 
      expression in a-ATN (64.38 +/- 19.22%, P < 0.05). The expression of alpha-SMA in 
      the tubulointerstitium, the number of interstitial TGF-beta(1)-positive cells and 
      the CTGF-positive interstitial area were all increased in both a-ATN and AA-ATN, 
      with no obvious differences between the two groups. With respect to extracellular 
      matrix (ECM) deposition, FN, Col-III and Col-IV were detected only in the 
      interstitium of AA-ATN. PTC lumina were decreased in size and misshapen in the 
      AA-ATN group. Also in AA-ATN, the luminal wall was partially disrupted, 
      endothelial cells were swollen and vacuoles and granules were found in the cell 
      plasma. Parts of the endothelial cells were detached from the tubular basement 
      membrane. CONCLUSION: The strong ability for RTEC repair after acute injury was 
      severely diminished in AA-ATN, and this effect may be partly due to reduced EGF 
      expression. Anti-fibrosis mechanisms may also be impaired in AA-ATN, since both 
      a-ATN and AA-ATN had increased expression of TGF-beta(1) and CTGF, whereas only 
      the latter group showed ECM deposition. Injury and loss of PTC occurred in 
      AA-ATN, and this may contribute to tubulointerstitial damage, the inability of 
      plerosis and the tendency towards fibrosis in this disease.
FAU - Yang, Li
AU  - Yang L
AD  - Renal Division, Department of Medicine, First Hospital, and Institute of 
      Nephrology, Peking University, Beijing 100034, P.R. China.
FAU - Li, Xiaomei
AU  - Li X
FAU - Wang, Haiyan
AU  - Wang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061123
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Actins)
RN  - 0 (Aristolochic Acids)
RN  - 0 (Biomarkers)
RN  - 0 (CCN2 protein, human)
RN  - 0 (Fibronectins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Mutagens)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (eye-derived growth factor)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - 94218WFP5T (aristolochic acid I)
SB  - IM
MH  - Actins/metabolism
MH  - Adult
MH  - Aristolochic Acids/*adverse effects
MH  - Biomarkers/metabolism
MH  - Biopsy
MH  - Connective Tissue Growth Factor
MH  - Disease Progression
MH  - Endothelium, Vascular/drug effects/ultrastructure
MH  - Female
MH  - Fibroblast Growth Factors/metabolism
MH  - Fibronectins/metabolism
MH  - Fibrosis/etiology/metabolism/pathology
MH  - Humans
MH  - Immediate-Early Proteins/metabolism
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Kidney Glomerulus/blood supply/drug effects/*ultrastructure
MH  - Kidney Tubular Necrosis, Acute/chemically induced/*complications/metabolism
MH  - Kidney Tubules/metabolism/*ultrastructure
MH  - Male
MH  - Microscopy, Electron
MH  - Middle Aged
MH  - Mutagens/*adverse effects
MH  - Proliferating Cell Nuclear Antigen/metabolism
MH  - Transforming Growth Factor beta1/metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2006/11/25 09:00
MHDA- 2007/07/10 09:00
CRDT- 2006/11/25 09:00
PHST- 2006/11/25 09:00 [pubmed]
PHST- 2007/07/10 09:00 [medline]
PHST- 2006/11/25 09:00 [entrez]
AID - gfl556 [pii]
AID - 10.1093/ndt/gfl556 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2007 Feb;22(2):445-56. doi: 10.1093/ndt/gfl556. Epub 
      2006 Nov 23.