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学科主题临床医学
Possible mechanisms explaining the tendency towards interstitial fibrosis in aristolochic acid-induced acute tubular necrosis
Yang, Li; Li, Xiaomei; Wang, Haiyan
关键词acute tubular necrosis aristolochic acid chinese herb fibrosis PTC
刊名NEPHROLOGY DIALYSIS TRANSPLANTATION
2007-02-01
DOI10.1093/ndt/gfl556
22期:2页:445-456
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Transplantation ; Urology & Nephrology
研究领域[WOS]Transplantation ; Urology & Nephrology
关键词[WOS]CHINESE HERBS ; RENAL-FAILURE ; GROWTH-FACTOR ; NEPHROTOXICITY ; NEPHROPATHY ; TOXICITY ; INJURY ; REPAIR
英文摘要

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.

语种英语
WOS记录号WOS:000243805400023
Citation statistics
Cited Times:62[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61144
Collection北京大学第一临床医学院_肾脏内科
作者单位1.Peking Univ, Inst Nephrol, Beijing 100034, Peoples R China
2.Peking Univ, Dept Med, Div Renal, Hosp 1, Beijing 100034, Peoples R China
Recommended Citation
GB/T 7714
Yang, Li,Li, Xiaomei,Wang, Haiyan. Possible mechanisms explaining the tendency towards interstitial fibrosis in aristolochic acid-induced acute tubular necrosis[J]. NEPHROLOGY DIALYSIS TRANSPLANTATION,2007,22(2):445-456.
APA Yang, Li,Li, Xiaomei,&Wang, Haiyan.(2007).Possible mechanisms explaining the tendency towards interstitial fibrosis in aristolochic acid-induced acute tubular necrosis.NEPHROLOGY DIALYSIS TRANSPLANTATION,22(2),445-456.
MLA Yang, Li,et al."Possible mechanisms explaining the tendency towards interstitial fibrosis in aristolochic acid-induced acute tubular necrosis".NEPHROLOGY DIALYSIS TRANSPLANTATION 22.2(2007):445-456.
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