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

Abstract

The role of reactive oxygen species (ROS) in the regulation of hair follicle cycle and skin homeostasis is poorly characterized. ROS have been traditionally linked to human disease and ageing, but recent findings suggest that 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 hair follicle, 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.

Dermal Papilla Cells and Melanocytes Response to Physiological Oxygen Levels Depends on Their Interactions 

“…Overall, these studies indicate that low oxygen levels are bene cial for DP cells and melanocytes, which seem to agree with the oxygen tension measured in the human DP (4.0-5.2% O 2 ) [24] or skin (average 5.3%O 2 ) [25]. Nevertheless, the anagen hair bulb is a ROS-enriched microenvironment [26], in which ROS directly activates proliferation and differentiation programs, stimulating hair growth [27]. Therefore, the involvement of multiple oxygen-associated responses, potentially by the different cells implicated in hair growth is expected, but yet to be elucidated.…”

“…Despite the generically accepted deleterious effects of supraphysiological ROS accumulation, there is a thin line separating bene cial and detrimental effects, which is associated to the tissues' physiological ROS levels. In the hair bulb, a transient and physiological elevation of ROS [26] is necessary to promote hair growth and differentiation programmes [27] during anagen. Interestingly, although ROS levels in cocultured hMel and DP were lower under physoxia than in normoxia, potentially as a consequence of the lower oxygen availability, they were higher than in the corresponding homotypic controls, which was observed independently of the oxygen level.…”

A primer for studying cell cycle dynamics of the human hair follicle

“…The cell cycle dynamics of murine hair follicles (HFs) during HF development and cycling have become progressively better defined over the past two decades (,s1–s4), and have recently been further illuminated by the introduction of instructive in vivo imaging techniques . In contrast, the cell cycle dynamics of the human HF are much less well understood, as they have only been investigated partially in vivo or within isolated or organ‐cultured anagen VI scalp HFs (that may be undergoing the early stages of HF regression (catagen)) (,s5).…”

Effect of dual‐drug‐releasing micelle–hydrogel composite on wound healing in vivo in full‐thickness excision wound rat model

“…As the radical concentration increases, so does the expression of SOD, a radical-scavenging enzyme. 64 Considering the antioxidant activity of curcumin, a model drug in the current study, we anticipated that oxidative stress in the wound should show a decreasing trend over the period of wound healing (Fig. 10).…”