Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein

Sarah X. Zhang, Joshua J. Wang, Azar Dashti, Kenneth Wilson, Ming Hui Zou, Luke Szweda, Jian Xing Ma, Timothy J. Lyons

Research output: Contribution to journalArticle

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Abstract

Oxidized and/or glycated low-density lipoprotein (LDL) may mediate capillary injury in diabetic retinopathy. The mechanisms may involve pro-inflammatory and pro-oxidant effects on retinal capillary pericytes. In this study, these effects, and the protective effects of pigment epithelium-derived factor (PEDF), were defined in a primary human pericyte model. Human retinal pericytes were exposed to 100 μg/ml native LDL (N-LDL) or heavily oxidized glycated LDL (HOG-LDL) with or without PEDF at 10-160 nM for 24 h. To assess pro-inflammatory effects, monocyte chemoattractant protein-1 (MCP-1) secretion was measured by ELISA, and nuclear factor-κB (NF-κB) activation was detected by immunocytochemistry. Oxidative stress was determined by measuring intracellular reactive oxygen species (ROS), peroxynitrite (ONOO-) formation, inducible nitric oxide synthase (iNOS) expression, and nitric oxide (NO) production. The results showed that MCP-1 was significantly increased by HOG-LDL, and the effect was attenuated by PEDF in a dose-dependent manner. PEDF also attenuated the HOG-LDL-induced NF-κB activation, suggesting that the inhibitory effect of PEDF on MCP-1 was at least partially through the blockade of NF-κB activation. Further studies demonstrated that HOG-LDL, but not N-LDL, significantly increased ONOO- formation, NO production, and iNOS expression. These changes were also alleviated by PEDF. Moreover, PEDF significantly ameliorated HOG-LDL-induced ROS generation through up-regulation of superoxide dismutase 1 expression. Taken together, these results demonstrate proinflammatory and pro-oxidant effects of HOG-LDL on retinal pericytes, which were effectively ameliorated by PEDF. Suppressing MCP-1 production and thus inhibiting macrophage recruitment may represent a new mechanism for the salutary effect of PEDF in diabetic retinopathy and warrants more studies in future.

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalJournal of Molecular Endocrinology
Volume41
Issue number3-4
DOIs
StatePublished - Sep 1 2008

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Pericytes
Oxidative Stress
Inflammation
Chemokine CCL2
Reactive Oxygen Species
Nitric Oxide Synthase Type II
Diabetic Retinopathy
LDL Lipoproteins
Nitric Oxide
oxidized low density lipoprotein
pigment epithelium-derived factor
Peroxynitrous Acid
Up-Regulation
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Macrophages
LDL glycosylated lipoproteins

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein. / Zhang, Sarah X.; Wang, Joshua J.; Dashti, Azar; Wilson, Kenneth; Zou, Ming Hui; Szweda, Luke; Ma, Jian Xing; Lyons, Timothy J.

In: Journal of Molecular Endocrinology, Vol. 41, No. 3-4, 01.09.2008, p. 135-143.

Research output: Contribution to journalArticle

Zhang, Sarah X. ; Wang, Joshua J. ; Dashti, Azar ; Wilson, Kenneth ; Zou, Ming Hui ; Szweda, Luke ; Ma, Jian Xing ; Lyons, Timothy J. / Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein. In: Journal of Molecular Endocrinology. 2008 ; Vol. 41, No. 3-4. pp. 135-143.
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AU - Szweda, Luke

AU - Ma, Jian Xing

AU - Lyons, Timothy J.

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