Lysophosphatidylserine Induces MUC5AC Production via the Feedforward Regulation of the TACE-EGFR-ERK Pathway in Airway Epithelial Cells in a Receptor-Independent Manneropen access
- Authors
- Sim, Myeong Seong; Kim, Hye Jeong; Jo, Sang Hee; Kim, Chun; Chung, Il Yup
- Issue Date
- Apr-2022
- Publisher
- Multidisciplinary Digital Publishing Institute (MDPI)
- Keywords
- airway epithelial cells; EGFR; MUC5AC; LysoPS; TACE; TGF-alpha; TLR2
- Citation
- International Journal of Molecular Sciences, v.23, no.7, pp 1 - 17
- Pages
- 17
- Indexed
- SCIE
SCOPUS
- Journal Title
- International Journal of Molecular Sciences
- Volume
- 23
- Number
- 7
- Start Page
- 1
- End Page
- 17
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/107910
- DOI
- 10.3390/ijms23073866
- ISSN
- 1661-6596
1422-0067
- 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-alpha 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 LysoPS 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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Collections - COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY > ERICA 의약생명과학과 > 1. Journal Articles
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