PC Project awarded Dr. Diana Blaydon of Queen Mary University of London a two-year £144,581 grant to make in vitro models for studying palmoplantar skin in PC. Below is a report on the work she has been doing:
Understanding PPK: Why Palm and Sole Skin Needs Its Own Science
Lay Summary
What we are doing and why it’s important
Palmoplantar keratodermas (PPKs) are rare inherited conditions of the skin that specifically affect palm and sole (palmoplantar) skin on your hands and feet. The skin becomes thickened and is often painful, particularly when walking, as in Pachyonychia Congenita (PC).
Palm and sole skin is quite different to the skin on the rest of the human body. However, most scientific research is conducted on body skin, including skin cells that are grown in the lab, and we have less understanding of how the specialized palmoplantar skin works and what goes wrong in PPK. With our research we are trying to bridge this gap in our knowledge by, firstly, generating human derived palm and sole cells to mimic either normal or PPK palmoplantar skin and, secondly, generating novel mouse models of PPK to understand how the skin condition develops and towards identifying /testing new therapies to alleviate the skin thickening and the pain.
What we’ve found so far
In our lab, we have been comparing the human skin cells taken from palmoplantar skin to body skin cells. We have found some differences between the two cell types in proteins that make up/regulate the internal skeleton (termed the “cytoskeleton” which is made primarily of different keratin proteins) within the skin cells. This is important as a cell’s cytoskeleton plays a crucial role in helping the cell resist/respond to mechanical insults, which palmoplantar skin is more exposed to. Also, inherited mutations in genes that make certain cytoskeleton proteins are the cause of some PPK conditions, such as PC. Early findings from our lab suggest that cell models of PC-K16 (a form of PC with mutations in the cytoskeleton keratin protein K16 gene), behave differently depending on whether they are made in body skin cells or palmoplantar cells. Therefore, we believe it is important to study PPK conditions in the right cell type – palmoplantar skin cells.
In addition, mouse models are being developed to mimic human PPK, but there are similarly very few studies on mouse paw skin. Using both publicly available data comparing human palmoplantar skin to body skin and our unique mouse datasets (generated with grant funding from the PC project), we have found that mouse paw skin shows many similarities to human palmoplantar skin. This is important as it gives our research team (and the PC research community) confidence in using these mouse models as a valuable tool for understanding what is going wrong in PPK and to help in the development of new therapies.
