Researchers have discovered that the Bpifb1 gene plays an important role in controlling levels of a mucin protein called MUC5B, one of the main components of mucus. This means that the gene also plays a crucial role in protecting the body’s airways.
The team found that deleting the Bpifb1 gene in lab mice led to higher levels of MUC5B.The findings suggest that it might be a possible target for future treatments to reduce the amount of mucus in the airways of cystic fibrosis (CF) patients.
The study, “Identification of trans Protein QTL for Secreted Airway Mucins in Mice and a Causal Role for Bpifb1,” was published in the journal Genetics.
“Other researchers at the UNC Marsico Lung Institute previously found that even a seemingly slight increase of mucins can lead to severe changes to mucus in human airways,” the study’s lead author, Samir Kelada, PhD, MPH, assistant professor of genetics at the University of North Carolina, Chapel Hill, said in a press release.
Despite the known importance of MUC5B, the genes controlling its levels of natural expression previously were unknown. The research team set out to identify the genes that are behind this natural variation in airway mucin levels. They performed a genetic analysis that pinpointed the Bpifb1 gene as a potential regulator of MUC5B.
Then, they deleted the gene in mice to verify that it is involved in the protein’s production. The researchers observed that when the mice lacked Bpifb1, they produced more MUC5B.
The team will now determine if their findings also apply to humans by examining whether genetic variation in the Bpifb1 gene relates to differences in mucus accumulation in patients with CF, asthma, and chronic obstructive pulmonary disease (COPD).
“Our finding shows that Bpifb1 plays a causative role in MUC5B levels in the airways. How exactly it does this is still not known, but our work suggests the gene is involved in regulating biophysical aspects of mucus, and this regulation is crucial to how well a person clears mucus,” Kelada said.
But the Bpifb1 gene will not be their only focus.
“In collaboration with investigators at the Marsico Lung Institute, we will be moving beyond gene discovery to using the Bpifb1 knockout mouse to explore fundamental aspects of mucus structure and function. Now the goal is to find ways to alter mucus so it becomes much less of a problem for people with these conditions.”
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