Most current treatments largely focus on suppressing autoimmune attacks and reducing inflammation, but if dormant melanocytes are still present in lesions that might change the way we treat the disease
Ichiro Katayama
These changes activate pathways that are commonly activated when cells are remodeling. In this process, the actin cytoskeleton of the cell is reorganized, gene expression is altered, including that of genes associated with an immature melanocyte state. The findings suggest a self-reinforcing cycle in which changes to the basement membrane drive melanocyte dedifferentiation, while the dedifferentiated melanocytes become less able to maintain a healthy basement membrane, further promoting the disease process.
“This was an exciting discovery for us, as most current treatments largely focus on suppressing autoimmune attacks and reducing inflammation, but if dormant melanocytes are still present in lesions that might change the way we treat the disease,” Professor Katayama said. “New treatment avenues such as reactivating existing cells or restoring their normal attachment to the basement membrane may be possible.”
When the researchers used pharmacological inhibitors targeting the signaling pathways activated by this adhesion switch, they were able to restore expression of mature melanocyte markers, recover pigmentation-related gene expression, and reverse many features of the dedifferentiated-like phenotype.
“This was an exciting aspect of our research, as it suggests that changing gene expression isn’t permanent and this process may be reversible,” Dr. Yang explained. “We found that drugs were able to restore melanocyte function and pigmentation-related characteristics. The next step will be to perform clinical studies to see if this approach is a viable way to manage the disease.”
Source: Osaka Metropolitan University