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Zhenhua Xu, Takeshi Yoshida, Debasish Maiti, Liudmila Cebotaru, Elia J. Duh; Myocyte Enhancer Factor 2C (MEF2C) Negatively Regulates Inflammation In Retinal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2795.
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Inflammation is important in multiple ocular diseases, including post-surgical macular edema and retinal vasculitis. Endothelial cells play a vital role in the inflammatory process, including interaction with leukocytes. The transcription factor MEF2C is widely expressed in endothelial cells and plays an important role in bone, muscle, and cardiovascular development. Our preliminary microarray data showed that MEF2C might be involved in the inflammatory process. The objective of this study was to determine the possible role of MEF2C in regulating inflammation in retina endothelial cells.
Human retinal endothelial cells (HRECs) were treated with TNF-α and the expression of MEF2C was assayed by real-time PCR and Western blot analysis. After knocking down MEF2C by siRNA transfection, the expression of pro-inflammatory genes was determined by real-time PCR. The functional relevance of MEF2C to inflammation was measured by in vitro leukocyte adhesion assay. NF-ΚB activation was assessed by nuclear translocation and gel electrophoretic mobility shift assay. Adenovirus-mediated MEF2C overexpression was performed to determine the effect of MEF2C on TNF-α-induced leukocyte adhesion.
TNF-α inhibited MEF2C expression and activity in retinal endothelial cells. Knockdown of MEF2C in endothelial cells resulted in the up-regulation of multiple pro-inflammatory genes and stimulated leukocyte adhesion to endothelial cells. Nuclear translocation and DNA-binding activity of NF-ΚB was induced by knockdown of MEF2C. Furthermore, overexpression of MEF2C in retinal endothelial cells significantly suppressed TNF-α-induced leukocyte adhesion.
These results indicate that MEF2C modulates the inflammatory response in endothelial cells and suggest that MEF2C is a novel negative regulator of inflammation in endothelial cells.
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