Honey-Mediated Wound Healing: H2O2 Entry through AQP3 Determines Extracellular Ca2+ Influx

International Journal of Molecular Sciences

Francesco Moccia¹  Umberto Laforenza²  Elia Ranzato³  Mauro Patrone⁴  Simona Martinotti⁴ 

[1] Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy;Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy;DiSIT—Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Piazza Sant’Eusebio 5, 13100 Vercelli, Italy;DiSIT—Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy;

关键词: AQP3;    Ca²⁺ signaling;    hydrogen peroxide;    honey;    wound healing;   

DOI  :  10.3390/ijms20030764

来源: DOAJ

【 摘 要 】

Since Biblical times, honey has been utilized in “folk medicine„, and in recent decades the positive qualities of honey have been re-discovered and are gaining acceptance. Scientific literature states that honey has been successfully utilized on infections not responding to classic antiseptic and antibiotic therapy, because of its intrinsic H₂O₂ production. In our study, we demonstrated the involvement of H₂O₂ as a main mediator of honey regenerative effects on an immortalized human keratinocyte cell line. We observed that this extracellularly released H₂O₂ could pass across the plasma membrane through a specific aquaporin (i.e., AQP3). Once in the cytoplasm H₂O₂, in turn, induces the entry of extracellular Ca²⁺ through Melastatin Transient Receptor Potential 2 (TRPM2) and Orai1 channels. Honey-induced extracellular Ca²⁺ entry results in wound healing, which is consistent with the role played by Ca²⁺ signaling in tissue regeneration. This is the first report showing that honey exposure increases intracellular Ca²⁺ concentration ([Ca²⁺]_i), due to H₂O₂ production and redox regulation of Ca²⁺-permeable ion channels, opening up a new horizon for the utilization of the honey as a beneficial tool.

【 授权许可】

Unknown