Mechanisms regulating progressive scarring in Chronic Kidney Disease
The international impact of our research has resulted in our group being asked to host the 12th International Conference of the International Society for Hyaluronan Sciences in June 2019. This conference will bring together clinicians and scientists from academia and industry from all over the world to meet and discuss recent advances in the basic science, clinical application and biotechnology of Hyaluronan, the molecule that binds to CD44 to promote scarring. Further info: https://www.ishas.org/
Chronic-kidney-disease (CKD) affects 15% of the UK population and increasing numbers of people worldwide. There is no cure for CKD and it is a relentlessly progressive disease. For many years our research group has focused on understanding the mechanisms controlling the scarring of the kidney that is characteristic of CKD. This scarring results from changes in the structure and functions of cells in the cortex of the kidney and our group is at the forefront of research aimed at finding treatments to prevent or even reverse these changes.
We have identified a grouping of several different proteins on the surface of cells that controls their scarring response and our main aims are:
- To investigate how these proteins interact with each other to give the cells their “scar-forming” identity
- To identify any other interactions that may be involved
- Examine ways to interfere with or disrupt the interactions identified to potentially develop therapeutic interventions to prevent or reverse the scarring process.
We have systematically investigated the scarring response of cells and have recently found that there is a protein, called CD44, that can exist in more than one form, each form having a different and distinct structure and function. It is central to the pro-scarring grouping of proteins and in its smallest form it promotes scarring. When expressed as a larger form, however, it can prevent or reverse the scarring changes. Which form of the protein is produced is dictated by another (unrelated) small cell surface protein that can enter the cell and travel to the nucleus where it attaches to genes to regulate the scarring process.
Current research is uncovering the mechanisms involved in these processes and how the anti-scarring activity of the large CD44 protein may be mimicked as a potential therapy.
We were the first group to describe the gene-regulating effect of the small protein in the nucleus and we intend to examine which parts of its structure control the expression of anti-scarring genes. We were also the first group to describe the anti-scarring potential of the large CD44 protein and we have now used systematic analysis of the protein to identify the sections that are central to this effect. Together with a commercial partner, the active sections of this protein are being made and tested for use as a potential anti-scarring therapy.
Although initially focussed on CKD, the results of our research are much more widely applicable. Scarring in any organ involves the same cell changes that we have described. If we are successful in developing our anti-scarring therapeutics, then they will likely be useful in other progressive diseases as well as in CKD.
Contacts: Dr Soma Meran and Dr Robert Steadman
Dr Soma Meran: https://www.cardiff.ac.uk/people/view/126571-meran-soma
Dr Robert Steadman:https://www.cardiff.ac.uk/people/view/126744-steadman-robert