title: Far-infrared protects vascular endothelial cells from advanced glycation end products-induced injury via PLZF-mediated autophagy in diabetic mice.
abstract: The accumulation of advanced glycation end products (AGEs) in diabetic patients induces vascular endothelial injury. Promyelocytic leukemia zinc finger protein (PLZF) is a transcription factor that can be activated by low-temperature far-infrared (FIR) irradiation to exert beneficial effects on the vascular endothelium. In the present study, we investigated the influence of FIR-induced PLZF activation on AGE-induced endothelial injury both in vitro and in vivo. FIR irradiation inhibited AGE-induced apoptosis in human umbilical vein endothelial cells (HUVECs). PLZF activation increased the expression of phosphatidylinositol-3 kinases (PI3K), which are important kinases in the autophagic signaling pathway. FIR-induced PLZF activation led to autophagy in HUVEC, which was mediated through the upregulation of PI3K. Immunofluorescence staining showed that AGEs were engulfed by HUVECs and localized to lysosomes. FIR-induced autophagy promoted AGEs degradation in HUVECs. In nicotinamide/streptozotocin-induced diabetic mice, FIR therapy reduced serum AGEs and AGEs deposition at the vascular endothelium. FIR therapy also reduced diabetes-induced inflammatory markers in the vascular endothelium and improved vascular endothelial function. These protective effects of FIR therapy were not found in PLZF-knockout mice. Our data suggest that FIR-induced PLZF activation in vascular endothelial cells protects the vascular endothelium in diabetic mice from AGE-induced injury.
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan.|Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.|Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taiwan.|School of Medicine, National Defense Medical Center, Taiwan.
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan.|Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taiwan.
authors.forename: Tso-Hsiao
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan.|Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.
authors.forename: Mei-Yi
authors.initials: MY
authors.lastname: Wu
authors.affiliation: Institute of Medical Sciences, Tzu Chi University, Taiwan.
authors.forename: Tz-Chong
authors.initials: TC
authors.lastname: Chou
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.
authors.forename: Jia-Rung
authors.initials: JR
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.
authors.forename: Meng-Jun
authors.initials: MJ
authors.lastname: Wei
authors.affiliation: Department of Electronic and Computer Engineering, National Taiwan University of Science and Technology, Taiwan.
authors.forename: San-Liang
authors.initials: SL
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Hong
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.
authors.forename: Cai-Mei
authors.initials: CM
authors.lastname: Zheng
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.
authors.forename: I-Jen
authors.initials: IJ
authors.lastname: Chiu
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan.|Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.
authors.forename: Yuh-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taiwan.
authors.forename: Ching-Min
authors.initials: CM
authors.lastname: Hsu
authors.affiliation: Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan.|Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taiwan.|School of Medicine, National Defense Medical Center, Taiwan.
authors.forename: Yung-Ho
authors.initials: YH
authors.lastname: Hsu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001343:Autophagy / Q000187:drug effects* / Q000528:radiation effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019610:Cytoprotection / Q000528:radiation effects*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology*; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007259:Infrared Rays; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects
chemical_list: D017127:Glycation End Products, Advanced; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse; C081628:advanced glycation end products-bovine serum albumin; C092037:ZBTB16 protein, human; D012710:Serum Albumin, Bovine; D019869:Phosphatidylinositol 3-Kinases