UV-Irradiation- and Inflammation-Induced Skin Barrier Dysfunction Is Associated with the Expression of Olfactory Receptor Genes in Human Keratinocytes.

Wesuk Kang, Bomin Son, Soyoon Park, Dabin Choi, Taesun Park
Author Information
  1. Wesuk Kang: Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea.
  2. Bomin Son: Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea.
  3. Soyoon Park: Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea.
  4. Dabin Choi: Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea.
  5. Taesun Park: Department of Food and Nutrition, BK21 FOUR, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea. ORCID

Abstract

Olfactory receptors (ORs) have diverse physiological roles in various cell types, beyond their function as odorant sensors in the olfactory epithelium. These previous findings have suggested that ORs could be diagnostic markers and promising therapeutic targets in several pathological conditions. In the current study, we sought to characterize the changes in the expression of ORs in the HaCaT human keratinocytes cell line exposed to ultraviolet (UV) light or inflammation, well-recognized stimulus for skin barrier disruption. We confirmed that major olfactory signaling components, including ORs, , , and adenylate cyclase type 3, are highly expressed in HaCaT cells. We have also demonstrated that the 12 ectopic ORs detectable in HaCaT cells are more highly expressed in UV-irradiated or inflamed conditions than in normal conditions. We further assessed the specific OR-mediated biological responses of HaCaT cells in the presence of known odorant ligands of ORs and observed that specific ligand-activated ORs downregulate skin barrier genes in HaCaT cells. This study shows the potential of OR as a marker for skin barrier abnormalities. Further research is needed to explore how OR is implicated in the development and progression of barrier dysfunction.

Keywords

References

  1. Front Mol Biosci. 2016 Jan 07;2:73 [PMID: 26779489]
  2. Phytother Res. 2015 Jul;29(7):1088-96 [PMID: 25881570]
  3. Int J Mol Sci. 2020 Apr 20;21(8): [PMID: 32326002]
  4. PLoS One. 2014 May 06;9(5):e96333 [PMID: 24800820]
  5. Int Immunopharmacol. 2020 Feb 20;82:106146 [PMID: 32088638]
  6. Int J Mol Sci. 2020 Apr 30;21(9): [PMID: 32366052]
  7. Nutrients. 2019 Dec 04;11(12): [PMID: 31817085]
  8. Cell Death Discov. 2016 May 09;2:16010 [PMID: 27551504]
  9. Arch Dermatol Res. 1996 Jun;288(7):383-90 [PMID: 8818186]
  10. Biochim Biophys Acta. 2014 Mar;1841(3):295-313 [PMID: 24252189]
  11. Exp Dermatol. 2017 Jul;26(7):569-576 [PMID: 28191688]
  12. PLoS One. 2013;8(2):e55368 [PMID: 23405139]
  13. Int J Mol Sci. 2013 Mar 26;14(4):6720-45 [PMID: 23531535]
  14. Front Physiol. 2018 May 16;9:456 [PMID: 29867524]
  15. J Ethnopharmacol. 2018 Jan 30;211:217-223 [PMID: 28970155]
  16. Chem Biodivers. 2014 Nov;11(11):1764-81 [PMID: 25408322]
  17. Front Pharmacol. 2020 Jul 07;11:1018 [PMID: 32733250]
  18. Front Biosci. 2000 Aug 01;5:D678-93 [PMID: 10922298]
  19. G Ital Dermatol Venereol. 2009 Dec;144(6):689-700 [PMID: 19907407]
  20. Physiol Rev. 2018 Jul 1;98(3):1739-1763 [PMID: 29897292]
  21. Int J Mol Sci. 2019 Feb 10;20(3): [PMID: 30744173]
  22. Exp Dermatol. 2008 Dec;17(12):1063-72 [PMID: 19043850]
  23. J Allergy Clin Immunol. 2019 May;143(5):1838-1848.e4 [PMID: 30445058]
  24. Mol Nutr Food Res. 2018 Aug;62(15):e1800173 [PMID: 29901851]
  25. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Apr;1864(4):489-499 [PMID: 30639733]
  26. J Invest Dermatol. 2014 Nov;134(11):2823-2832 [PMID: 24999593]
  27. Br J Dermatol. 1986 Mar;114(3):319-27 [PMID: 3954952]
  28. Sci Rep. 2017 Aug 25;7(1):9471 [PMID: 28842679]
  29. Nat Genet. 2013 Jun;45(6):580-5 [PMID: 23715323]
  30. Pharmacol Res. 2018 Mar;129:443-452 [PMID: 29155016]
  31. Front Oncol. 2019 Nov 11;9:1210 [PMID: 31781505]
  32. J Cell Physiol. 2018 Mar;233(3):2104-2115 [PMID: 28338216]
  33. Photochem Photobiol. 1999 Mar;69(3):317-21 [PMID: 10089823]
  34. Molecules. 2020 Mar 28;25(7): [PMID: 32231089]
  35. Am J Physiol Renal Physiol. 2019 Feb 1;316(2):F372-F381 [PMID: 30484350]
  36. Neuron. 2014 Feb 19;81(4):847-59 [PMID: 24559675]
  37. J Invest Dermatol. 1985 Apr;84(4):272-6 [PMID: 3981040]
  38. Int J Mol Sci. 2017 Oct 10;18(10): [PMID: 28994699]
  39. Exp Dermatol. 2017 Jan;26(1):58-65 [PMID: 27315375]
  40. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17111-6 [PMID: 23027968]
  41. Postepy Dermatol Alergol. 2014 May;31(2):84-91 [PMID: 25097473]
  42. Photodermatol Photoimmunol Photomed. 1991 Jun;8(3):129-34 [PMID: 1804292]
  43. Arch Biochem Biophys. 2018 May 1;645:72-80 [PMID: 29559321]
  44. Sci Rep. 2019 Dec 13;9(1):19029 [PMID: 31836740]
  45. Cytotechnology. 2007 Jun;54(2):77-83 [PMID: 19003021]
  46. Front Physiol. 2017 Nov 30;8:888 [PMID: 29249973]
  47. J Clin Invest. 2017 Nov 1;127(11):4118-4123 [PMID: 28990936]
  48. Mediators Inflamm. 2017;2017:7435621 [PMID: 29391667]
  49. J Dtsch Dermatol Ges. 2015 Nov;13(11):1119-23 [PMID: 26513068]
  50. Allergy Asthma Immunol Res. 2018 May;10(3):207-215 [PMID: 29676067]
  51. Cell. 1980 Apr;19(4):1033-42 [PMID: 6155214]
  52. Front Physiol. 2016 Aug 04;7:339 [PMID: 27540365]
  53. Int J Mol Sci. 2020 Sep 07;21(18): [PMID: 32906658]

Grants

  1. 2019R1A2C2003340/National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)

MeSH Term

Adenylyl Cyclases
Cell Line
GTP-Binding Protein alpha Subunits
GTP-Binding Protein alpha Subunits, Gs
Gene Expression Regulation
Humans
Inflammation
Keratinocytes
Receptors, Odorant
Signal Transduction
Skin
Ultraviolet Rays

Chemicals

GTP-Binding Protein alpha Subunits
Receptors, Odorant
olfactory G protein subunit alpha olf
GTP-Binding Protein alpha Subunits, Gs
RIC8B protein, human
Adenylyl Cyclases
adenylate cyclase 3

Word Cloud

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