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.
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.
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.
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.
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We would like to thank Dr. He Chen, Department of Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University for providing us with Serum biochemical analysis.
This project was supported by the National Natural Science Foundation of China (nos. 81700522, 81602344), the fund of Anhui medical university doctoral start research (no. 0601067101), Anhui Provincial Natural Science Foundation (1704a0802161, 1808085MH235). Soft science project of Anhui provincial science and technology department (1607a0202062).
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The data analysed during the current study are available from the corresponding author on reasonable request.
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The animal testing procedures have been approved by the Code of Ethics and reviewed and implemented according to the guidelines of the Animal Care and Use Committee of Anhui Medical University (number: LLSC20150348).
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Li, L., Yang, C., Li, S. et al. TMEM88 modulates the secretion of inflammatory factors by regulating YAP signaling pathway in alcoholic liver disease. Inflamm. Res. 69, 789–800 (2020). https://doi.org/10.1007/s00011-020-01360-y
- RAW264.7 cells