What is it about?
Receptor for advanced glycation endproducts (RAGE) is involved in several pathophysiological process, including diabetes, cardiovascular diseases, and inflammation. RAGE is expressed in cell surface, and its level is dynamically regulated both by expression and shedding. Shedded RAGE is present in the human circulation, and may modulate the toxic RAGE signaling through a decoi mechanism. However, cellular and molecular mechanisms underlying RAGE shedding is still to be veiled. In this study, we showed, by using endothelial specific RAGE transgenic mice and normal human endothelial cells, that RAGE shedding is under the control of inflammatory signaling. We found two major platforms, JNK and ATF4 systems together with sheddases ADAM10 and MMP9, are essential for TNF-α-stimulated human endothelial cells. Our finding could provide us with a novel aspect and target for regulation of inflammatory disorders.
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Why is it important?
In addition to the significant impact of RAGE on inflammatory augmentation, molecular mechanisms for inflammation mediated-RAGE shedding is clearly demonstrated.
Perspectives
The findings provide us with a novel aspect and target for regulation of inflammatory disorders.
Hidenori Koyama
Hyogo Ika Daigaku
Read the Original
This page is a summary of: JNK and ATF4 as two important platforms for tumor necrosis factor-α–stimulated shedding of receptor for advanced glycation end products, The FASEB Journal, November 2018, Federation of American Societies For Experimental Biology (FASEB),
DOI: 10.1096/fj.201701553rr.
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