Photoactivation of ROS production in situ transiently activates cell proliferation in mouse skin and in the hair follicle stem cell niche promoting hair growth and wound healing

The role of reactive oxygen species (ROS) in the regulation of hair follicle (HF) cycle and skin homeostasis is poorly characterized. ROS have been traditionally linked to human disease and aging, but recent findings suggest that they can also have beneficial physiological functions in vivo in mammals. To test this hypothesis, we transiently switched on in situ ROS production in mouse skin. This process activated cell proliferation in the tissue and, interestingly, in the bulge region of the HF, a major reservoir of epidermal stem cells, promoting hair growth, as well as stimulating tissue repair after severe burn injury. We further show that these effects were associated with a transient Src kinase phosphorylation at Tyr416 and with a strong transcriptional activation of the prolactin family 2 subfamily c of growth factors. Our results point to potentially relevant modes of skin homeostasis regulation and demonstrate that a local and transient ROS production can regulate stem cell and tissue function in the whole organism.JE was supported by Spanish MINECO grants SAF11-23493 and RTC-2014-2626-1 and Comunidad Autónoma de Madrid grant SkinModel CAM S10/BMD-2359. DV and MRH were supported by US NIH grant R01AI050875. AJ was supported by Spanish MINECO grant FIS PI12/01253 and CAM S10/BMD-2359. JCS was supported by Spanish MCINN grant CTQ2010-20870-C03-03. EC and MIC were supported by Spanish MECD-FPU and UAM-FPI fellowships, respectively.Peer reviewe