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Insulin-like growth factor-binding protein-3 mediates high glucose-induced apoptosis by increasing oxidative stress in proximal tubular epithelial cells.

Abstract：

:IGF-binding protein-3 (IGFBP-3) is the major circulating carrier protein for IGF, and also acts as a potent antiproliferative agent in various cell types. Recently, IGFBP-3 was reported to mediate high glucose-induced apoptosis in mesangial cells and podocytes. In this study, we investigated the role of IGFBP-3 in high glucose-induced apoptosis in proximal tubular epithelial cells (PTEC). Expression of IGFBP-3 protein and mRNA in a porcine PTEC line (LLC-PK1 cells) was measured after exposure to either standard (5.5 mM) or high-glucose (30 mM) medium. We quantified apoptosis after treatment with small interfering RNA against IGFBP-3 (siRNA:IGFBP-3) in high-glucose medium or in cells that overexpressed IGFBP-3. Oxidative stress was measured in high-glucose medium, in the presence of siRNA:IGFBP-3, or in IGFBP-3-overexpressing cells. IGFBP-3 protein and mRNA expression in LLC-PK1 cells was higher in high-glucose medium than in standard-glucose medium. Exposure to high-glucose medium increased apoptosis, and high-glucose-induced apoptosis was abolished by siRNA:IGFBP-3. IGFBP-3 overexpression induced apoptosis in LLC-PK1 cells. Both high-glucose medium and IGFBP-3 overexpression increased reactive oxygen species, and siRNA:IGFBP-3 reduced this increase. Antioxidant treatment decreased IGFBP-3 expression and apoptosis, whereas oxidative stress from hydrogen peroxide increased IGFBP-3 expression, suggesting that oxidative stress increases IGFBP-3 expression. Our results suggest that increased IGFBP-3 expression by high glucose mediates high-glucose-induced apoptosis in PTEC. Increased oxidative stress from high glucose enhances IGFBP-3 expression, inducing apoptosis. Increased expression of IGFBP-3 by high glucose induces additional oxidative stress, which may result in amplification of hyperglycemic damage.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Yoo EG,Lee WJ,Kim JH,Chae HW,Hyun SE,Kim DH,Kim HS,Oh Y

doi

10.1210/en.2010-1122

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

3135-42

issue

eissn

0013-7227

issn

1945-7170

pii

en.2010-1122

journal_volume

152

pub_type

杂志文章

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Insulin-like growth factor-binding protein-3 mediates high glucose-induced apoptosis by increasing oxidative stress in proximal tubular epithelial cells.