Molecular signals initiating reactions in wounded skin
It only takes a few seconds for skin to get wounded. But before wound healing processes can be observed in the tissue, very often several hours are passing by. This leads to an important question: what exactly is happening in the skin between the damage and the healing of the wound? SHoW´s biomedical research team has developed a new explanatory approach for this unresolved issue. This blog post gives insights into the scientists´ current findings. One aspect good to know in advance: biology and orchestral music have more in common than you might think.
Both a buzz of voices and excitement are characteristic for a concert hall before a classical orchestra enters the stage. Only a very short time before the concert finally starts, the soundscape changes drastically and silence is spreading. There are always a few isolated coughs breaking this expectant silence. Then the musicians enter the hall, and they take their seats following a precisely defined distribution plan. The role each instrument or musician takes on within the orchestra is clearly aligned. When the conductor finally joins the orchestra on stage, the time has come for the concert to begin. Ladies and gentlemen, music please!
But: what does this situation have to do with SHoW´s biomedical research? What is the connection between a wound, its bleeding and healing and a classic concert? We now hope for an expectant silence spreading among our audience. The following text will provide you with biological details of the fascinating processes in the skin, which is in a state of emergency due to an injury.
Healthy cells respond to wounding
If the skin is wounded, bleeding will follow immediately after. These events happen within a very short time – in presto, if we continue using musical vocabulary. However, several hours might pass by before the processes of wound healing can be observed in the tissue. It is still widely unknown what exactly is going on in the skin between the wounding and the healing and how the cells react to these sudden changes. Therefore, SHoW´s biomedical researchers are working intensively on the period between the damaging of the tissue and healing processes to be visible. Nadja Ring, Helene Dworak and colleagues in the research group of Mikolaj Ogrodnik have documented so far, that as a result of an injury in the skin of pigs, the ribosomal protein S6 (rpS6) is activated within minutes in a precisely defined zone surrounding the wound. For getting rpS6 activated in this area, a phosphate group is attached to the protein. This process is defined as phosphorylation, which fulfils an important regulatory function within cells. By means of the activation of rpS6 shortly after the injury, healthy cells surrounding the wound signalise to the tissue that the current situation requires an immediate reaction. The skin is then “translating” these signals into wound healing processes.
Parallelisms in music and biology
Like in a well-rehearsed classic orchestra, the cells in wounded porcine skin each take on their specific roles. During a concert, musicians interact with each other and convert the notes on the sheets in front of them into music. Within damaged skin, the tissue “interprets” the activation of rpS6 in healthy cells surrounding the wound and “translates” these molecular signals into wound healing processes. In both cases, the outcome can only be successful if the communication between the protagonists (cells or musicians) is functioning. If so, the result will be a healed wound or a melodious concert.
We will further continue focusing solely on the biological processes in damaged skin. The orchestra is leaving us here, both music and applause have faded away. We will now draw the curtain up for further details from our biomedical research group.
Activation zone forms, independently of the wound´s cause
In their experimental work, the scientists have shown so far that the activation of rpS6 in porcine skin occurs in different types of wounds. This clearly defined area obviously appears in the vicinity of damaged tissue, regardless of the cause of injury. For example, in a burn, the activation zone forms in parallel with the surface. It is located below the part of the skin, where cells are dying because of the burn. These cells die uncontrollably, because of the extreme stress the tissue is facing. During this process, the protein HMGB1 is spreading from the nucleus of the cells into their plasma. In general, HMGB1 indicates to the body that a pathological damage has occurred. Beneath the area containing HMGB1, SHoW´s biomedical researchers have located a zone containing active caspase 3. This enzyme is essential when a cell is undergoing apoptosis, a programmed cell death. In this way, cells are dying without affecting neighbouring cells. In porcine skin damaged by a burn, the area showing the activated protein rpS6 starts precisely where cells are undergoing apoptosis. This area is also going deeper into the tissue, which demonstrates, that not only dying cells are active there, but also the healthy ones.
If porcine skin is injured by a cut, the rpS6 activation zone runs along this cut. In this case too, healthy cells react in parallel to the wound. If the tissue is damaged by the prick of a needle, the activation zone is located around the resulting canal.
Of pigs, mice and men
The researchers have so far not only demonstrated that healthy cells surrounding a wound in porcine skin communicate the need for a reaction to the tissue shortly after a damage. This zone characterized by the activation of the ribosomal protein S6 is also forming in the skin of mice. For these mammals, the researchers have been able to observe the processes in wounded skin over a longer period. So, they have documented that if the skin of mice is injured, the activation of rpS6 also happens within the keratinocytes. These are specialised cells in the uppermost layer of the skin. Keratinocytes form the epithelial tongue, which grows into the wound from its edges. The epithelial tongue will eventually cover the wounded skin entirely. Moreover, the rpS6 activation zone in the wounded skin of mice shows many markers especially characteristic for the processes of wound healing. These processes include cell proliferation, the formation of vessels and senescence. If cells become senescent, they can no longer divide or multiply, because the cell cycle is arrested. Looking at the damaged skin of mice, senescent cells can only be found in the area of the wound containing activated rpS6.
Last but not least, Nadja Ring, Helene Dworak and colleagues under the lead of Mikolaj Ogrodnik have been able to prove that as a result of a damage, the rpS6 activation zone also forms in human skin. These experimental results are very promising for further research into wound healing processes.
Scientific publication underway
SHoW´s biomedical researchers are currently working intensively on publishing their findings in a scientific journal. They have already made their new approach available publicly, using the online platform “bioRxiv”. This database contains newest scientific articles that have not yet undergone the complex assessment process of academic publishing.
