The discovery of a rare cell in the lining of the lungs has shed light on the organ-wide response necessary to repair damage caused by toxins such as those found in wildfire smoke or respiratory viruses. Stanford Medicine researchers, in collaboration with their colleagues, have uncovered a crucial process involving neuroendocrine cells that play a key role in initiating a biological cascade to protect insulin-producing pancreatic islet cells from harm.
Published in the journal Cell, the research highlights the potential of treating the airways of mice with an experimental drug that activates the repair pathway. This treatment has shown to protect the airways from damage following infection with influenza or the virus responsible for COVID-19. Conversely, blocking the pathway resulted in more severe damage to the airways in affected animals.
The researchers believe that activating the signaling pathway initiated by airway or pancreatic neuroendocrine cells in humans could enhance the ability of individuals, such as firefighters and those with respiratory illnesses, to avoid permanent lung damage. Additionally, it may help prevent individuals with metabolic syndrome from progressing to diabetes.
According to Philip Beachy, Ph.D., a professor at Stanford University, the signaling cascade involved in this process serves to both protect and regenerate vulnerable cells in the airway and pancreas. Disruption of this circuit can lead to significant damage, including the loss of specialized airway cells and impaired stem cell division for repair.
While the study was conducted in mice, there are indications of a similar pathway in humans. Patients treated with a cancer drug that inhibits the pathway have shown an increased risk of developing diabetes post-treatment, suggesting the potential protective role of activating this pathway in individuals with metabolic syndrome.
Neuroendocrine cells, comprising less than 1% of the total cells in the airway lining, play a crucial role in sensing oxygen levels, modulating immune responses, and initiating repair processes. The solitary neuroendocrine cells found in the tracheal airway have long puzzled researchers, as their exact function was unclear until now.
The research also delves into the involvement of the Hedgehog protein family in the repair process. Beachy’s lab identified the Desert hedgehog protein in the solitary neuroendocrine cells, which triggers a signaling cascade leading to the protection and regeneration of specialized cells in the lung epithelium. This epithelial-mesenchymal feedback loop plays a vital role in safeguarding the airway cells from damage and promoting their repair.
Overall, the study highlights the importance of the Desert hedgehog signaling pathway in orchestrating the repair and regeneration of damaged tissues in the lungs and pancreas. The researchers are now exploring ways to activate this pathway in humans to prevent lung damage from airborne toxins and mitigate the risk of diabetes in at-risk individuals.
Collaborators from the University of California, San Francisco, also contributed to this groundbreaking research, paving the way for potential therapeutic interventions targeting this protective process.
