The cellular mechanism of chronic pruritus or pruritus, which severely affects patients with liver disease, primary cholangitis (PBC), It was discovered by a group of researchers from the UNAM Institute for Cellular Physiology (IFC), through joint work with colleagues from the United States, Germany and Poland.
“The chronic itching in these patients is disabling and affecting their quality of life, to the point that they require a liver transplant.. It is an autoimmune disease that damages the bile duct and generates digestive problems. ” Tamara Lottie Rosenbaum Amir, IFC Researcher and Head of the UNAM Project.
The scientist and her peers started the study from the interaction of lysophosphatidylcholine (LPC)), Which is a fat produced in different parts of the body, the TRPV4 ion channel, and is associated with perception of changes in the temperature of the environment and some substances.
“We are in the process of obtaining an international patent for this knowledge, to suggest this channel as a therapeutic target It would be beneficial for this type of disease that affects people’s quality of life. “
The study was published in a newspaper article Digestive system diseases, With which they collaborated Rosenbaum Amir, researcher Sarah Luz Morales-Lazaro, also from the International Finance Corporation, and former master’s student Anna Elena Lopez Romero.
Based on numerous experiments, the undergraduate student and her peers found that the LPC was able to open the TRPV4 channel and they identified the exact region that regulates the opening and closing of the channel. This reaction activates the physiological process of itching.
“We show that in patients with cholangitis, the LPC is increased, and so is the LPC interaction with the TRPV4 channel, which activates it, opens it up (such as opening the diaphragm of an imaging camera to allow the passage of light) It allows the passage of calcium ions that generate a signal. Thus, microRNA vesicles activating the TRPV1 channel (from the same family as the TRPV4 channel) are released. He explained that these signals are transmitted by skin cells to nerve cells near this organ and from there to the brain, causing itching.
The interaction between LPC and TRPV4 allows calcium to enter the cell, triggering a series of q eventsThis leads to the vesicles coming out.
These vesicles contain a specific molecule of RNA – a small portion of single-stranded RNA., Which in this mechanism acts as a message between skin cells and sensory neurons. “The signal that originates in the skin is transmitted to the nerve cells that relay information to the brain and is processed as an itch, and this work shows us the complete blueprint for how itching starts on the skin,” Rosenbaum Amir elaborates.
The research described the exact biophysics of how the channel is activated, the exact amino acids that interact with it in the channel structure, as well as the biochemistry that leads to this process. “It has also been shown that when LPC and fine RNA (present in the vesicles) are injected into monkeys, this itch reaction occurs.Added.
The work also showed that TRPV4 may be a therapeutic target as the channel as such can be blocked from Try to avoid itching or block the delicate RNA that carries the signal to the brain, the specialist explained.