Lysophosphatidylserine Induces MUC5AC Production via the Feedforward Regulation of the TACE-EGFR-ERK Pathway in Airway Epithelial Cells in a Receptor-Independent Manner |
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Authors: | Myeong Seong Sim Hye Jeong Kim Sang Hee Jo Chun Kim Il Yup Chung |
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Affiliation: | 1.Department of Bionano Technology, Hanyang University, Ansan 15588, Korea; (M.S.S.); (H.J.K.);2.Department of Molecular and Life Sciences, College of Science and Convergence Technology, Hanyang University, Ansan 15588, Korea; |
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Abstract: | Lysophosphatidylserine (LysoPS) is an amphipathic lysophospholipid that mediates a broad spectrum of inflammatory responses through a poorly characterized mechanism. Because LysoPS levels can rise in a variety of pathological conditions, we sought to investigate LysoPS’s potential role in airway epithelial cells that actively participate in lung homeostasis. Here, we report a previously unappreciated function of LysoPS in production of a mucin component, MUC5AC, in the airway epithelial cells. LysoPS stimulated lung epithelial cells to produce MUC5AC via signaling pathways involving TACE, EGFR, and ERK. Specifically, LysoPS- dependent biphasic activation of ERK resulted in TGF-α secretion and strong EGFR phosphorylation leading to MUC5AC production. Collectively, LysoPS induces the expression of MUC5AC via a feedback loop composed of proligand synthesis and its proteolysis by TACE and following autocrine EGFR activation. To our surprise, we were not able to find a role of GPCRs and TLR2, known LyoPS receptors in LysoPS-induced MUC5AC production in airway epithelial cells, suggesting a potential receptor-independent action of LysoPS during inflammation. This study provides new insight into the potential function and mechanism of LysoPS as an emerging lipid mediator in airway inflammation. |
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Keywords: | airway epithelial cells, EGFR, MUC5AC, LysoPS, TACE, TGF-α , TLR2 |
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