TMEM88 mediates inflammatory cytokines secretion by regulating JNK/P38 and canonical Wnt/β-catenin signaling pathway in LX-2 cells

摘要

Recent data have shown that Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane, interacts with the PDZ domain of disheveled-1 (Dvl-1) in Xenopus embryos. Indeed, TMEM88 might inhibit the canonical Wnt/β-catenin signaling pathway by competing with LRP5/6 for interaction with Dvl-1. TMEM88 plays a crucial role in regulating human stem cell differentiation and embryonic development. Until recently, the function of TMEM88 has been a matter of debate. In this study, we explore the role of TMEM88 in cytokine secretion and the role of the MAPK and Wnt/β-catenin signaling pathway in tumor necrosis factor-alpha (TNF-α)-induced TMEM88 expression in LX-2 cells. We demonstrated that overexpression of TMEM88 results in an upregulation of IL-6 and IL-1β secretion. On the other hand, knockdown of TMEM88 by transfecting siRNA decreased IL-6 and IL-1β secretion in LX-2 cells. Meanwhile, the results showed that TMEM88 silencing could increase the expression levels of canonical Wnt/β-catenin accompanied with upregulated phosphorylation of wnt3a, wnt10b and β-catenin protein levels in response to TNF-α. In conclusion, these results indicated that TMEM88 plays a significant role in TNF-α-enhanced cytokine (IL-6 and IL-1β) secretion of LX-2 cells via regulating JNK/P38 and canonical Wnt/β-catenin signaling pathway.