The p-rpS6-zone delineates wounding responses and the healing process
Nadja Ring, Helene Dworak, Barbara Bachmann, Barbara Schädl, Karla Valdivieso, Tomaz Rozmaric, Patrick Heimel, Ines Fischer, Eirini Klinaki, Aniko Gutasi, Kornelia Schuetzenberger, Gabriele Leinfellner, James Ferguson, Susanne Drechsler, Michael Mildner, Markus Schosserer, Paul Slezak, Oded Meyuhas, Флориан Грубер, Johannes Grillari, Heinz Redl, Mikołaj Ogrodnik
Abstract
The spatial boundaries of tissue response to wounding are unknown. Here, we show that in mammals, the ribosomal protein S6 (rpS6) is phosphorylated in response to skin injury, forming a zone of activation surrounding the region of the initial insult. This p-rpS6-zone forms within minutes after wounding and is present until healing is complete. The zone is a robust marker of healing as it encapsulates features of the healing process, including proliferation, growth, cellular senescence, and angiogenesis. A mouse model that is unable to phosphorylate rpS6 shows an initial acceleration of wound closure, but results in impaired healing, identifying p-rpS6 as a modulator but not a driver of healing. Finally, the p-rpS6-zone accurately reports on the status of dermal vasculature and the effectiveness of healing, visually dividing an otherwise homogeneous tissue into regions with distinct properties.