Indoxyl Sulfate Induces Epithelial-to-Mesenchymal Transition in Rat Kidneys and Human Proximal Tubular Cells

被引：68
|
作者：
Bolati, Dilinaer
Shimizu, Hidehisa
Higashiyama, Yukihiro [2 ]
Nishijima, Fuyuhiko [2 ]
Niwa, Toshimitsu [1 ]
机构：
[1] Nagoya Univ, Grad Sch Med, Dept Adv Med Uremia, Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Kureha Co, Biomed Res Labs, Tokyo, Japan
来源：
AMERICAN JOURNAL OF NEPHROLOGY | 2011年 / 34卷 / 04期
关键词：
Indoxyl sulfate; Epithelial-to-mesenchymal transition; Chronic kidney disease; Uremic toxin; OSTEOBLAST-SPECIFIC PROTEINS; SMOOTH-MUSCLE-CELLS; OXIDATIVE STRESS; MYOFIBROBLAST TRANSITION; ENDOTHELIAL-CELLS; TIGHT JUNCTION; PROGRESSION; FIBROSIS; PROLIFERATION; EXPRESSION;
D O I：
10.1159/000330852
中图分类号：
R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];
学科分类号：
1002 ; 100201 ;
摘要：
Background/Aims: Indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). This study aimed to determine if IS induces epithelial-to-mesenchymal transition (EMT) in the kidneys of hypertensive rats and human proximal tubular cells (HK-2). Methods: EMT was evaluated by immunohistochemistry, reverse transcription-polymerase chain reaction and immunoblotting of the epithelial markers E-cadherin and zonula occludens-1 (ZO-1), and the mesenchymal marker alpha-smooth muscle actin (alpha-SMA). Rat groups consisted of (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive IS-administered rats (DN+IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive IS-administered rats (DH+IS). HK-2 cells were incubated with or without IS. Results: In kidneys, DH rats showed reduced expression of E-cadherin and ZO-1, and enhanced expression of alpha-SMA compared with DN rats. DN+IS and DH+IS rats showed reduced expression of E-cadherin and ZO-1, and enhanced expression of alpha-SMA compared with DN and DH rats, respectively. DH+IS and DH rats showed increased Masson's trichrome-positive fibrosis areas compared with DH and DN, respectively. IS-treated HK-2 cells showed reduced expression of E-cadherin and ZO-1, and enhanced expression of alpha-SMA. Conclusion: IS induces EMT in the kidneys of hypertensive rats and in human proximal tubular cells. Copyright (C) 2011 S. Karger AG, Basel
引用
收藏
页码：318 / 323
页数：6
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