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Invest Ophthalmol Vis Sci. 2012 Jun 8;53(7):3481-9. doi: 10.1167/iovs.11-9076.

ERK1/2 signaling pathway in the release of VEGF from Müller cells in diabetes.

Author information

  • 1EENT Hospital, Eye Institute, Fudan University, Shanghai, China.

Abstract

PURPOSE:

Diabetic retinopathy (DR) is one of the most serious complications of diabetes and has become a major blinding eye disease, but its treatment remains unsatisfactory. The ERK1/2 signaling pathway has been shown to participate in regulating secretion of VEGF in DR from our previous studies. The role of VEGF in the development of DR provides a target for treatment. Our present research focuses on Müller cells, a major source of VEGF secretion, to investigate the role of ERK1/2 signaling pathway on regulation of VEGF release in diabetes.

METHODS:

Immunofluorescence was used to observe the ERK1/2 phosphorylation activity on early diabetic rat retinal Müller cells. Müller cells were stimulated by high glucose in vitro. Western blot and immunohistochemistry were used to determine ERK1/2 signaling pathway expression and phosphorylation. AP-1 DNA binding activity status was monitored by electrophoretic mobility shift assay (EMSA). ELISA and PCR monitored VEGF secretion. Inhibition of ERK1/2 phosphorylation with U0126 was observed for changes in VEGF secretion.

RESULTS:

Phos-ERK1/2 was expressed on Müller cells early in diabetes. In vitro high glucose stimulation of Müller cells increased VEGF secretion with a peak at 24 hours. An ERK1/2 specific inhibitor, U0126, stopped the phosphorylation of ERK1/2, lowered AP-1 DNA binding activity, and reduced Müller cells secretion of VEGF under high glucose conditions.

CONCLUSIONS:

ERK1/2 signaling pathway has some role in regulating Müller cells secretion of VEGF in DR. Targeting the ERK1/2 signaling pathway in Müller cells through intervention of the upstream signaling pathway or nuclear transcription factors of VEGF secretion could be a type of anti-VEGF treatment for DR.

PMID:
22511624
[PubMed - indexed for MEDLINE]
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