Liang-Yun Li1, Chen-Chen Yang1,2, Su-Wen Li3, Yu-Min Liu1,4, Hao-Dong Li1, Shuang Hu1, Hong Zhou1,5, Jin-Liang Wang2, Hang Shen3, Xiao-Ming Meng1, Jun Li1, Tao Xu6. 1. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, China. 2. Hefei Fourth People's Hospital, Affiliated Psychological Hospital of Anhui Medical University, Anhui Medical University, Hefei, 230000, China. 3. First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, 230000, China. 4. Department of Immunology, Anhui Medical University, Hefei, China. 5. Division of Life Sciences and Medicine, Department of Pharmacy, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230031, Anhui, China. 6. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, China. xutao@ahmu.edu.cn.
Abstract
OBJECTIVE: Transmembrane protein 88 (TMEM88), a new protein of increasing concern existed in cell membrane, inhibits the typical Wnt/β-catenin signaling pathway to play a regulatory role on cell proliferation by binding to Dishevelled-1. Until recently, the connection between TMEM88 and alcoholic liver disease is unknown. In this research, we explored the effect of TMEM88 on the secretion of inflammatory cytokines in ethanol (EtOH)-induced RAW264.7 cells, moreover, the function of YAP signaling pathway in EtOH-induced RAW264.7 cells were investigated. METHODS: We administered TMEM88 adenovirus (ADV-TMEM88) by tail vein injection into C57BL/6J mice in vivo. In vitro, RAW264.7 murine macrophages were stimulated with EtOH and were transfected with pEGFP-C1-TMEM88 and TMEM88 siRNA, respectively, protein expression and mRNA expression of IL-6 and IL-1β were assessed by Western Blotting and RT-qPCR, respectively. RESULTS: Our group found that the overexpression of TMEM88 led to an up-regulation of IL-6 and IL-1β secretion, hinting that it had the possibility of linking with the initiation, the development, and the end of inflammation. In addition to that, TMEM88 silencing reduced the secretion of IL-6 and IL-1β in RAW264.7 cells. Moreover, we demonstrated that the YAP signaling pathway under the action of EtOH was activated by TMEM88. CONCLUSIONS: All in all, these experimental outcomes indicated that TMEM88 had an indispensable impact on EtOH-induced secretion of inflammatory cytokines (IL-6 and IL-1β) in RAW264.7 cells through YAP signaling pathway.
OBJECTIVE:Transmembrane protein 88 (TMEM88), a new protein of increasing concern existed in cell membrane, inhibits the typical Wnt/β-catenin signaling pathway to play a regulatory role on cell proliferation by binding to Dishevelled-1. Until recently, the connection between TMEM88 and alcoholic liver disease is unknown. In this research, we explored the effect of TMEM88 on the secretion of inflammatory cytokines in ethanol (EtOH)-induced RAW264.7 cells, moreover, the function of YAP signaling pathway in EtOH-induced RAW264.7 cells were investigated. METHODS: We administered TMEM88adenovirus (ADV-TMEM88) by tail vein injection into C57BL/6J mice in vivo. In vitro, RAW264.7murine macrophages were stimulated with EtOH and were transfected with pEGFP-C1-TMEM88 and TMEM88 siRNA, respectively, protein expression and mRNA expression of IL-6 and IL-1β were assessed by Western Blotting and RT-qPCR, respectively. RESULTS: Our group found that the overexpression of TMEM88 led to an up-regulation of IL-6 and IL-1β secretion, hinting that it had the possibility of linking with the initiation, the development, and the end of inflammation. In addition to that, TMEM88 silencing reduced the secretion of IL-6 and IL-1β in RAW264.7 cells. Moreover, we demonstrated that the YAP signaling pathway under the action of EtOH was activated by TMEM88. CONCLUSIONS: All in all, these experimental outcomes indicated that TMEM88 had an indispensable impact on EtOH-induced secretion of inflammatory cytokines (IL-6 and IL-1β) in RAW264.7 cells through YAP signaling pathway.