Characterization of the cell physiological effect of olfactory receptors in wound healing

• Applicants: Professor Dr. Hanns Hatt; Dr. Lea Weber
• Subject Area: Dermatology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445110810

Olfactory receptors (ORs) are expressed in several human tissues, where they have a variety of functions in physiological and pathophysiological processes. The potential of ORs is also reflected in wound healing processes. In human skin, an OR was detected that induces proliferation of skin cells. Due to the use of skin care products, the skin is permanently exposed to odorants, although the effect of permanent exposure is hardly understood. The proposed project comprises the investigation of the effect of ligand-induced activation of ORs in the human skin. This approach aims to address the major components leading to impaired wound healing, which are the suppression of cell proliferation and migration as well as the bacterial colonization of the wound, by the use of odorants. Therefore, the ligands of the ORs showing an increased expression in human skin are first of all investigated with regard to their effect on wound healing. We focus on the receptors identified via next generation sequencing, which are OR5P3, OR7A5, OR2W3 and OR2H2 with their ligands (+)-carvone, (-)-carvone, 1-hexanol, 1-heptanol, 1-octanol, acetophenone, vertomugal, 4-methylvaleric acid, nerol and aldehyde 13-13. In addition, we aim to deorphanize the highly expressed receptor OR7C1 and characterize it functionally.First data reveal an increase in cell vitality of HaCaT cells upon application of carvone. After the investigation of the effect of the odorants on cell monolayers, the impact on 3D wound models as well as native skin from abdominoplasty will be investigated. The observed effects will be analyzed in calcium imaging experiments with regard to the underlying signal transduction cascade. In addition to the broadening of the general knowledge of ectopically expressed ORs in the human skin, this also offers the opportunity for a specific application of odorants, depending on the receptor expression pattern in the particular skin area.

• DFG Programme: Research Grants