Hsing Ru Tien

National Chung Hsing University, 臺中市, Taiwan, Taiwan

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Publications (2)12.56 Total impact

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    ABSTRACT: In response to aggravation by activated microglia, IL-13 can significantly enhance endoplasmic reticulum stress induction, apoptosis, and death via reciprocal signaling through C/EBPα and C/EBPβ. This reciprocal signaling promotes neuronal survival. Since the induction of COX-2 and PPARγ/HO-1 by IL-13 plays a crucial role in the promotion of and protection from activated microglia respectively, here we investigated the role of IL-13 in regulating C/EBPs in activated microglia and determined its correlation with neuronal function. The results revealed that IL-13 significantly enhanced C/EBPα/COX-2 expression and PGE2 production in LPS-treated microglial cells. Paradoxically, IL-13 abolished C/EBPβ/PPARγ/HO-1 expression. IL-13 also enhanced ER stress-evoked calpain activation by promoting the association of C/EBPβ and PPARγ. SiRNA-C/EBPα effectively reversed the combined LPS-activated caspase-12 activation and IL-13-induced apoptosis. In contrast, siRNA-C/EBPβ partially increased microglial cell apoptosis. By NeuN immunochemistry and CD11b staining, there was improvement in the loss of CA3 neuronal cells after intra-hippocampal injection of IL-13. This suggests that IL-13-enhanced PLA2 activity regulates COX-2/PGE2 expression through C/EBPα activation. In parallel, ER stress-related calpain downregulates the PPARγ/HO-1 pathway via C/EBPβ and leads to aggravated death of activated microglia via IL-13, thereby preventing cerebral inflammation and neuronal injury. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 07/2013; · 4.97 Impact Factor
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    ABSTRACT: N(ε) -carboxymethyllysine (CML), a major advanced glycation end product, plays a crucial role in diabetes-induced vascular injury. The roles of protein tyrosine phosphatases and vascular endothelial growth factor (VEGF) receptors in CML-related endothelial cell injury are still unclear. Human umbilical vein endothelial cell (HUVEC) is a commonly used human EC type. Here, we tested the hypothesis that NADPH oxidase/reactive oxygen species (ROS)-mediated SH2 domain-containing tyrosine phosphatase-1 (SHP-1) activation by CML inhibits the VEGF receptor-2 (VEGFR-2, KDR/Flk-1) activation, resulting in HUVEC injury. CML significantly inhibited cell proliferation and induced apoptosis and reduced VEGFR-2 activation in parallel with the increased SHP-1 protein expression and activity in HUVECs. Adding recombinant VEGF increased forward biological effects, which were attenuated by CML. The effects of CML on HUVECs were abolished by SHP-1 siRNA transfection. Exposure of HUVECs to CML also remarkably escalated the integration of SHP-1 with VEGFR-2. Consistently, SHP-1 siRNA transfection and pharmacological inhibitors could block this interaction and elevating [(3) H]thymidine incorporation. CML also markedly activated the NADPH oxidase and ROS production. The CML-increased SHP-1 activity in HUVECs was effectively attenuated by antioxidants. Moreover, the immunohistochemical stainings of SHP-1 and CML were increased, but phospho-VEGFR-2 staining was decreased in aortic endothelium of streptozotocin-induced and high-fat diet-induced diabetic mice. We conclude that a pathway of tyrosine phosphatase SHP-1-regulated VEGFR-2 dephosphorylation through NADPH oxidase-derived ROS is involved in the CML-triggered endothelial cell dysfunction/injury. These findings suggest new insights into the development of therapeutic approaches to reduce diabetic vascular complications. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    The Journal of Pathology 05/2012; · 7.59 Impact Factor