ERK5 Contributes to VEGF Alteration in Diabetic Retinopathy.pdfVIP

Hindawi Publishing Corporation Journal of Ophthalmology Volume 2010, Article ID 465824, 11 pages doi:10.1155/2010/465824 Research Article ERK5 Contributes to VEGF Alteration in Diabetic Retinopathy Yuexiu Wu, Yufeng Zuo, Rana Chakrabarti, Biao Feng, Shali Chen, and Subrata Chakrabarti Department of Pathology, Schulich School of Medicine, University of Western Ontario, London, ON, Canada N6A 5A5 Correspondence should be addressed to Subrata Chakrabarti, subrata.chakrabarti@schulich.uwo.ca Received 15 December 2009; Revised 15 April 2010; Accepted 19 May 2010 Academic Editor: Susanne Mohr Copyright © 2010 Yuexiu Wu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Diabetic retinopathy is one of the most common causes of blindness in North America. Several signaling mechanisms are activated secondary to hyperglycemia in diabetes, leading to activation of vasoactive factors. We investigated a novel pathway, namely extracellular signal regulated kinase 5 (ERK5) mediated signaling, in modulating glucose-induced vascular endothelial growth factor (VEGF) expression. Human microvascular endothelial cells (HMVEC) were exposed to glucose. In parallel, retinal tissues from streptozotocin-induced diabetic rats were examined after 4 months of follow-up. In HMVECs, glucose caused initial activation followed by deactivation of ERK5 and its downstream mediators myocyte enhancing factor 2C (MEF2C) and Kruppel- like factor 2 (KLF2) mRNA expression. ERK5 inactivation further led to augmented VEGF mRNA expression. Furthermore, siRNA mediated ERK5 gene knockdown suppressed MEF2C and KLF2 expression and increas