title: Mesenchymal Stem Cells Ameliorated Glucolipotoxicity in HUVECs through TSG-6.
abstract: Glucolipotoxicity is one of the critical causal factors of diabetic complications. Whether mesenchymal stem cells (MSCs) have effects on glucolipotoxicity in human umbilical vein endothelial cells (HUVECs) and mechanisms involved are unclear. Thirty mM glucose plus 100 μM palmitic acid was used to induce glucolipotoxicity in HUVECs. MSCs and HUVECs were co-cultured at the ratio of 1:5 via Transwell system. The mRNA expressions of inflammatory factors were detected by RT-qPCR. The productions of reactive oxygen species (ROS), cell cycle and apoptosis were analyzed by flow cytometry. The tumor necrosis factor-α stimulated protein 6 (TSG-6) was knockdown in MSCs by RNA interference. High glucose and palmitic acid remarkably impaired cell viability and tube formation capacity, as well as increased the mRNA expression of inflammatory factors, ROS levels, and cell apoptosis in HUVECs. MSC co-cultivation ameliorated these detrimental effects in HUVECs, but no effect on ROS production. Moreover, TSG-6 was dramatically up-regulated by high glucose and fatty acid stimulation in both MSCs and HUVECs. TSG-6 knockdown partially abolished the protection mediated by MSCs. MSCs had protective effects on high glucose and palmitic acid induced glucolipotoxicity in HUVECs, and TSG-6 secreted by MSCs was likely to play an important role in this process.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; West China Hospital, Sichuan University, Chengdu 610041, China. idealangelan@163.com.
authors.forename: Xingxing
authors.initials: X
authors.lastname: An
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; West China Hospital, Sichuan University, Chengdu 610041, China. findingclover@sohu.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; West China Hospital, Sichuan University, Chengdu 610041, China. chenyounan@scu.edu.cn.|School of Biomedical Sciences, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, WA 6845, Australia. chenyounan@scu.edu.cn.
authors.forename: Younan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Sichuan Neo-Life Stem Cell Biotech Inc. Chengdu 610041, China. luoai1239@sina.com.cn.
authors.forename: Ai
authors.initials: A
authors.lastname: Luo
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada. zyni8@hotmail.com.
authors.forename: Zuyao
authors.initials: Z
authors.lastname: Ni
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; West China Hospital, Sichuan University, Chengdu 610041, China. liujingping@scu.edu.cn.
authors.forename: Jingping
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; West China Hospital, Sichuan University, Chengdu 610041, China. yimianfenzi@163.com.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; West China Hospital, Sichuan University, Chengdu 610041, China. smmcuco@hotmail.com.
authors.forename: Meimei
authors.initials: M
authors.lastname: Shi
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; West China Hospital, Sichuan University, Chengdu 610041, China. cb0402022@sina.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; West China Hospital, Sichuan University, Chengdu 610041, China. longd37@126.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; West China Hospital, Sichuan University, Chengdu 610041, China. jqcheng@scu.edu.cn.
authors.forename: Jingqiu
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Ministry of Health; West China Hospital, Sichuan University, Chengdu 610041, China. luyanrong@scu.edu.cn.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005947:Glucose / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism; D019308:Palmitic Acid / Q000633:toxicity*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C072273:TNFAIP6 protein, human; D019308:Palmitic Acid; D005947:Glucose
keywords: HUVECs; MSCs; glucolipotoxicity; inflammation; tumor necrosis factor-α stimulated protein 6 (TSG-6)