- European Research Project
- May 1, 2023 - April 30, 2025
The skin isthe widest organ of the human body. Despite this, the mechanismsthat underline itsregulation are relatively poorly understood. Many skin diseases are characterized by defects in the control of lining renewal or reestablishing barrier integrity after the disruption. Thus, dissecting the signals that underpin the maintenance of skin homeostasis and regeneration are of pivotal interest for medicine. Recently, redox signaling as described to have a crucial role in these processes: indeed, H2O2 -the major signaling molecule of redox biology- is not only an essential second messenger, involved in skin proliferative and survival pathways but also it is reported that mild ER stress cursing with an increase in organelle redox potential is needed for efficient reepithelization. Recently, we have shown the presence of different ER-linked H2O2
luxes that orchestrate cellular redox responses in normal conditions and after the induction of
ER stress in HeLa cell lines. In this scenario, I propose to unveil the compartment-specific H2O2 fluxes that regulate the redoxstasis during keratinocytes differentiation with particular emphasis on those that arrive from the Endoplasmic Reticulum (ER). Indeed, the ER is one of the major contributors to cellular redoxstasis harboring sources, internal regulators, and distributors that vehicle redox signals back and forth to the ER. In particular, I divide this project into two main aims I) Characterize the role of intracellular redox fluxes during keratinocytes differentiation both in 2D and in 3D models II) Identify the interactors of ER-derived H2O2 flux in skin cell lines and characterize the downstream pathways. Importantly, a systematic analysis of the timing, thresholds, and targets of redox signals in skin pathways is a paramount gap in the field that has not yet been tackled, and thus constitutes the principal aim that this project wants to undertake.
- skin;redox signaling;h2o2;flux;differentiation