Abstract
Brush cells at the gastric groove have been proposed to operate as sensory cells capable of sensing constituents of ingested food. Recent studies have indicated that these cells express GPR120 (also known as FFAR4), the G protein-coupled receptor for long-chain fatty acids (LCFAs). However, functional implications of this receptor in brush cells have remained elusive. Here, we show that a great proportion of brush cells express GPR120. We used phosphorylation of the extracellular signal-regulated kinases 1/2 (ERK1/2) as a readout to monitor brush cell responses to the LCFAs oleic acid and α-linolenic acid. Our results demonstrate that ERK1/2 phosphorylation is increased upon exposure to both fatty acids. Increased ERK1/2 phosphorylation is accompanied by upregulated mRNA and protein levels of cyclooxygenase 2 (COX-2), a key enzyme for prostaglandin biosynthesis. Immunohistochemical experiments confirmed that oleic acid caused ERK1/2 phosphorylation and induced COX-2 expression in brush cells. Our results indicate that LCFA sensing elicits a signaling process in brush cells that may be relevant for a local regulation of gastric functions.
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Abbreviations
- ALA:
-
α-Linolenic acid
- COX-1:
-
Cyclooxygenase 1
- COX-2:
-
Cyclooxygenase 2
- DAPI:
-
4′,6-Diamidino-2-phenylindole
- DIC:
-
Differential interference contrast
- ERK1/2:
-
Extracellular signal-regulated kinases 1/2
- FA:
-
Fatty acids
- FFAR:
-
Free fatty acid receptor
- GPCR:
-
G protein-coupled receptor
- LCFA:
-
Long-chain fatty acid
- PLCβ2:
-
Phospholipase C β2
- TRPM:
-
Transient receptor potential cation channel, subfamily M, member 5
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Acknowledgements
We thank Kerstin Bach for her excellent technical assistance and Marilena Lieber for her skillful experimental support and advice. We would like to express our gratitude to T. Gudermann and V. Chubanov for generously providing the TRPM5 antibody.
Funding
This work was supported by the Deutsche Forschungsgemeinschaft, BR 712/25-1, BO 1743/3 and SFB/TR152.
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All applicable international (Council Directive 2010/63EU of the European Parliament and the Council of 22 September 2010 on the protection of animals used for scientific purposes), national (work was approved by the Committee on the Ethics of Animal Experiments at the Regierungspräsidium Stuttgart V318/14 PHY) and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (University of Hohenheim Animal Welfare Officer T125/14 PHY, T126/14 PHY).
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Widmayer, P., Hischer, L., Hennemann, K. et al. Long-chain fatty acid-induced intracellular signaling in GPR120-expressing brush cells at the limiting ridge of the murine stomach. Cell Tissue Res 376, 71–81 (2019). https://doi.org/10.1007/s00441-018-2972-1
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DOI: https://doi.org/10.1007/s00441-018-2972-1