Once developed, therapies that block TRPV4 may help treat or prevent inflammation in patients with rosacea, according to new research funded by the National Rosacea Society (NRS).
In earlier research, the team led by Dr. Anna Di Nardo, associate professor of medicine of the University of California-San Diego, had determined that mast cells, located at the interface between the nervous system and vascular system, were a missing link between rosacea triggers and inflammation. They found that mast cells play a direct role in the activation of certain types of cathelicidins.
Studying the process in mice, Dr. Di Nardo’s team determined that when exposed to a neuropeptide called PACAP, mast cells produce enzymes that trigger the production of cathelicidins. In mice bred to lack mast cells, however, this chain reaction did not occur.
Continuing their research, the scientists have now discovered that one of the proteins in cell membranes that facilitates communication between cells, known as transient receptor potential vanilloid 4 (TRPV4), plays a key role in activating mast cells in the skin of people with rosacea.
In the new study, the researchers first examined whether cathelicidins were involved in spurring general TRPV production. Two days after injecting cathelicidins into mice bred to exhibit human-like rosacea symptoms, they saw significant increases in the expression of both TRPV2 and TRPV4. The researchers then tested the findings in the laboratory (in vitro) in both mouse and human mast cell cultures, confirming that cathelicidin increases the expression of TRPV4 and also determining that TRPV4 regulates the inflammation caused by mast cells.
Dr. Di Nardo's team further identified a protein receptor on mast cells known as MRGX2 as the likely pathway to TRPV4 activation by cathelicidins. By turning off MRGX2 in mast cells, they were able to prevent TRPV4 from reacting to cathelicidins, which in turn prevented the mast cells from triggering an inflammatory immune response associated with rosacea.
“Although more work needs to be done, these findings suggest that potential therapies may be developed specifically to block TRPV4 as a direct means of treating or preventing inflammation in patients with rosacea,” Dr. Di Nardo says in a news release.
The new study appears in the Journal of Investigational Dermatology.