Airway Smooth Muscle Relaxant Finally Identified

By Patrick Yang ’20

Figure 1. Asthma’s exaggerated contraction of airways is due to a lack of smooth muscle relaxant.

Figure 1. Asthma’s exaggerated contraction of airways is due to a lack of smooth muscle relaxant.

Asthma, characterized by its iconic inhalers and abrupt episodes of coughing and wheezing, affects approximately 334 million people worldwide. The inflammatory disease is caused by the prolonged contraction of airway smooth muscles, which triggers difficulty with breathing. Despite our understanding of asthma’s symptoms, the mechanism behind asthma is still a mystery. Scientists speculate that normal airway epithelium, or cells composing the surface of a body cavity, secrete a compound that relaxes the airway after contraction – the epithelium-derived smooth muscle relaxing factor (EDSMRF). Despite numerous candidates for this relaxing factor, the actual factor still eludes scientists. Using the recent discovery of significant decrease of the protein, BPIFA1, found in asthmatics’ sputa (coughed up mucus), Dr. Robert Tarran of the University of North Carolina and his colleagues sought to determine if BPIFA1 was an EDSMRF.

The researchers examined the airway smooth muscle of mice with the BPIFA1 gene (BPIFA1+/+ mice) and mice without the BPIFA1 gene (BPIFA1-/- mice). Methacholine, a smooth muscle contractor, was given to the mice to test for correlation between presence of BPIFA1 and abnormal smooth muscle activity. In support of their hypothesis, results showed that BPIFA1-/- mice had significantly more airway resistance than their BPIFA1+/+ littermates. To further evidence of BPIFA1’s role in airway relaxation, tracheae excised from these mice were mounted onto myographs, which measure contractility. In a similar fashion as the previous procedure, a smooth muscle contractor was given to the tracheae and contractility was measured. It was discovered that tracheae of BPIFA1-/- mice almost tripled the contraction force of tracheae of BPIFA1+/+ mice. As confirmation of BPIFA1’s role in airway relaxation, contractility of BPIFA1-/- tracheae was measured before and after treatment with BPIFA1 protein. Results revealed that contractile force was reduced by more than half, which confirms that BPIFA1 is an EDSMRF.

Discovering BPIFA1’s smooth muscle relaxing trait contributes greatly to our understanding of asthma. Because asthmatics do not produce this protein, immediate treatments can now include BPIFA1 protein, alongside the medicine in inhalers, while future therapy can involve returning BPIFA1 producing-functionality to airway epithelial cells. A permanent solution to asthma may be on its way.

 

References:

  1. T. Wu, et al., Identification of bpifa1/splunc1 as an epithelium-derived smooth muscle relaxing factor. Nature 8, (2017). doi: 10.1038/ncomms14118.
  2. Image retrieved from: https://commons.wikimedia.org/wiki/File:Asthma_(Lungs).png
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