Lysophosphatidylserine Induces MUC5AC Production via the Feedforward Regulation of the TACE-EGFR-ERK Pathway in Airway Epithelial Cells in a Receptor-Independent Manner
| Autor: | Myeong Seong Sim, Hye Jeong Kim, Sang Hee Jo, Chun Kim, Il Yup Chung |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Inflammation
MAP Kinase Signaling System Organic Chemistry Epithelial Cells General Medicine Respiratory Mucosa respiratory system Mucin 5AC Catalysis Computer Science Applications Inorganic Chemistry ErbB Receptors airway epithelial cells EGFR MUC5AC LysoPS TACE TGF-α TLR2 Humans Physical and Theoretical Chemistry Lysophospholipids Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 7; Pages: 3866 |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|