Organ regeneration one step closer with new understanding of skin repair

Organ regeneration one step closer with new understanding of skin repair
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A team of scientists has brought the possibility of organ regeneration one step closer by shedding new light on how skin repairs itself.

The team from The University of Manchester has demonstrated how the activation of specific parts of DNA leads to better division of human skin cells. They have shown that two transcription factors – the proteins that bind DNA – were able to enhance the natural process of skin cell division.

The study, which was funded by the Medical Research Council and the Helmut Horten Foundation, has been published in Nucleic Acid Research.

Cell division

Typically, one in every fourth cell isolated from the inner layer of the skin divides, however, in the study the team was able to achieve an increase of this division by 20 to 25% without the addition of growth factors – which are proteins that regulate cellular growth.

The team instead used sulpharaphane, a compound found in broccoli, Brussels sprouts, and cabbages, which activates the binding of transcriptions factors to specific parts of the DNA which control cell division.

While most of the research was done on human cells isolated directly from donor skin, mouse models with genetically modified transcription factors were essential to prove the DNA-mediated mechanism.

Dr Svitlana Kurinna who led the study said: “We know that the skin sometimes cannot efficiently repair itself but the endogenous mechanism we discovered uses the body’s own processes to induce division of cells in the skin.

“Our findings suggest that the combined activity of both transcription factors is important to maintain the proliferative capacity of these cells (keratinocytes). Our skin can be easily damaged, which impacts the quality of life and in some cases, is life-threatening. However, we hope that this study provides some crucial insight into the process and lays the foundation for an exciting future investigating similar mechanisms in other organs.”

The research focusses on “basal” keratinocytes that represent the most inner growing layer, as well as on the layers closer to the surface of the skin – called supra basal – which can also play a crucial role in the healing process. The researchers say that the over promotion of cell division in basal layer could create the conditions for skin cancer, but the activation of the supra basal layer may be ‘cancer-proof.’

One of the identified transcription factors is the master regulator of the DNA in skin cells, while the other alleviates oxidative stress which is a result of reactive oxygen species from the environment, toxins, and the inner metabolic processes. Together, the transcription factors may protect and improve cell division without transforming them into cancer cells.

Kurinna added: “At the moment, once tissue becomes fibrotic and scarred, there’s no way of reversing it to fully functional state. Our ultimate goal is to improve regeneration of functional skin – and maybe other organs with a similar endogenous mechanism. Each organ has a different master regulator of the DNA, which works with the stress response, so we need to keep researching the mechanisms for specific treatments.”

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