April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Pro-inflammatory Wnt5a Gene Transcription Is Regulated By Neuroprotectin D1 In Retinal Epithelial Cells: A Pro-survival Signaling Pathway
Author Affiliations & Notes
  • Jorgelina M. Calandria
    Neuroscience Center, LSU Health Sciences Center, New Orleans, Louisiana
  • Nicolas G. Bazan
    Neuroscience Center, LSU Health Sciences Center, New Orleans, Louisiana
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 22. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Jorgelina M. Calandria, Nicolas G. Bazan; Pro-inflammatory Wnt5a Gene Transcription Is Regulated By Neuroprotectin D1 In Retinal Epithelial Cells: A Pro-survival Signaling Pathway. Invest. Ophthalmol. Vis. Sci. 2011;52(14):22.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: : NPD1 inhibits the expression of pro-inflammatory genes and enhances the expression of anti-apoptotic proteins of the Bcl-2 family (Mukherjee et al. 2004; Lukiw et al. 2005) as part of a pro-survival response elicited by the cells under oxidative stress stimulation. These events are integrated to influence the RPE cell fate. We hypothesized that NPD1 signaling regulate the expression of a key set of genes that are effectors in the inflammatory response.

Methods: : To determine if NPD1 was capable of influence gene expression triggered by oxidative stress, we performed a genome wide gene expression assessment using Affymetrix U133 plus 2.0 data on more than three hundred NPD1-regulated genes. We compared the expression of more than 70000 human genes on normal and 15-LOX-1 silenced ARPE-19 cells undergoing OS when they were treated with 50nM NPD1.

Results: : Gene Go analysis of the data showed a network of genes related with the Wnt5a/calcium signaling pathway (p< 0.05) and the possible involvement of Notch. As effector of Notch/Hedgehog, Hes1 is transcriptional modulator of Wnt related gene expression. Hes1 is 2.6 folds up-regulated by OS while NPD1 brought the levels to -3.4 folds of regulation related to the control. Accordingly, Wnt5a was found to follow a similar pattern of expression (OS up-regulated by 2.3 folds and NPD1downregulated by -3.8 folds). This pattern was found to be present at the protein level as well. Moreover, Wnt pathway transcriptional regulators NFATC4 and HNF4A are up-regulated from -9.85 and -1.37 in oxidative stress to -4.79 and 2.45 respectively when cell were treated by NPD1 using Real-Time PCR array targeting human transcription factors. As target of the global Notch/Hedgehog and Wnt regulation emerged in the network obtained from the gene array data EGR1 nuclear receptor up-regulated one order of magnitude by NPD1 and its regulation was confirmed by Real time PCR. The action of EGR1 was implicated in the regulation observed of VEGF-A and calcipressin.

Conclusions: : These data all together points to NPD1 targeting a specific set of master genes that underlie the anti-apoptotic and anti-inflammatory NPD1 bioactivity.

Keywords: lipids • retinal pigment epithelium • inflammation 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×