TMEM100 mediates inflammatory cytokines secretion in hepatic stellate cells and its mechanism research

• Published in: Toxicology letters Vol. 317; pp. 82 - 91
• Main Authors: Pan, Lin-xin, Li, Liang-yun, Zhou, Hong, Cheng, Shu-qi, Liu, Yu-min, Lian, Pan-pan, Li, Li, Wang, Le-le, Rong, Shan-jie, Shen, Chuan-pu, Li, Jun, Xu, Tao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-12-2019
• Subjects: ERK; IL-1β; IL-6; JNK; p38; TMEM100; TNF-α; TMEM100; TNF-α; p38; JNK; IL-1β; IL-6; ERK
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2018.12.010

•TMEM100 is decreased in human liver fibrosis tissues.•TMEM100 is down regulated by TNF-α in LX-2 Cells.•Effect of overexpression and knockdown of TMEM100 in LX-2 Cells.•Effect of TMEM100 on proliferation in TNF-α-treated LX-2 Cells.•TMEM100 is critical for the cytokine secretion of activated LX-2 Cells.•Effect of TMEM100 on MAPK signal pathway activity in TNF-α-treated LX-2.
Recent studies have shown that Transmembrane protein 100 (TMEM100) is a gene at locus 17q32 encoding a 134-amino acid protein with two hypothetical transmembrane domainsa, and first identified as a transcript from the mouse genome. As a downstream target gene of bone morphogenetic protein (BMP)-activin receptor-like kinase 1 (ALK1) signaling, it was activated to participate in inducing arterial endothelium differentiation, maintaining vascular integrity, promoting cell apoptosis, inhibiting metastasis and proliferation of cancer cells. However, evidence for the function of TMEM100 in inflammation is still limited. In this study, we explore the role of TMEM100 in inflammatory cytokine secretion and the role of MAPK signaling pathways in tumor necrosis factor-alpha (TNF-α)-induced TMEM100 expression in LX-2 cells. We found that the expression of TMEM100 was decreased markedly in human liver fibrosis tissues, and its expression was also inhibited in LX-2 cells induced by TNF-α, suggesting that it might be associated with the development of inflammation. Therefore, we demonstrated that overexpression of TMEM100 by transfecting pEGFP-C2-TMEM100 could lead to the down-regulation of IL-1β and IL-6 secretion. Moreover, we found that expression changes of TMEM100 could be involved in inhibition or activation of MAPK signaling pathways accompanied with regulating phosphorylation levels of ERK and JNK protein in response to TNF-α. These results suggested that TMEM100 might play an important role in the secretion of inflammatory cytokines (IL-1β and IL-6) of LX-2 cells induced by TNF-α, and MAPK (ERK and JNK) signaling pathways might participate in its induction of expression.