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

Abstract

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.

Activated NLR family pyrin domain containing 3 (NLRP3) inflammasome in keratinocytes promotes cutaneous T-cell response in patients with vitiligo

“…22 Notably, a recent study further observed activated TRPM2 in keratinocytes under oxidative stress. 23 Based on these findings, we hypothesize that oxidative stress can activate the NLRP3 inflammasome in keratinocytes through TRPM2, which enhances the cutaneous T-cell response in patients with vitiligo.…”

Bee Products in Dermatology and Skin Care

“…Honey induced extracellular Ca 2+ entry results in wound healing. It is similar to role plays by Ca 2+ signaling in tissue regeneration [47]. Moreover honey regulates the process of epithelial mesenchymal transition (EMT) and it has a positive impact on wound healing.…”

Endothelial TRPV1 as an Emerging Molecular Target to Promote Therapeutic Angiogenesis

“…It has, therefore, been suggested that optical stimulation of P3HT polymer induces the production of singlets and charge states, which in turn reduce oxygen dissolved in the medium to form superperoxide. Furthermore, superperoxide leads to the generation of hydrogen peroxide (H 2 O 2 ), which can permeate the plasma membrane through specific aquaporins (e.g., aquaporin 3) and thereby activate TRPV1 [44,207,217]. Overall, this work evidenced how the combined use of optical excitation and organic polymers technology can open interesting perspectives for the modulation of progenitor cells fate and, more generally, corroborated the idea that controlling the signaling pathways driving ECFC proliferation, differentiation, and tube formation may represent a reliable strategy to improve the regenerative outcome of therapeutic angiogenesis.…”