TMEM88 modulates the secretion of inflammatory factors by regulating YAP signaling pathway in alcoholic liver disease

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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.
Funding Information
  • National Natural Science Foundation of China (81700522, 81602344)
  • Anhui Provincial Natural Science Foundation (1704a0802161, 1808085MH235)

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