Deficient Zinc Transport in Lungs Linked to COPD, Cystic Fibrosis, Study Finds

José Lopes, PhD avatar

by José Lopes, PhD |

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Zinc deficiency in the lung causes overproduction of mucus and is associated with respiratory diseases such as chronic obstructive pulmonary disease (COPD), a new Japanese study shows.

The research study, “Zinc Deficiency via a Splice Switch in Zinc Importer ZIP2/SLC39A2 Causes Cystic Fibrosis-Associated MUC5AC Hypersecretion in Airway Epithelial Cells,” was published in the journal EBioMedicine, and was led by researchers at Kumamoto University in Japan.

In the United States, data from the National Institutes of Health shows that 12 million adults are diagnosed with COPD, with about 120,000 deaths each year. Six times more men than women die of COPD. In Japan, the number of COPD patients over age 40 with COPD is about 5.3 million.

COPD and cystic fibrosis (CF) are respiratory diseases characterized by chronic airway inflammation and obstruction, accompanied by exaggerated mucus retention and fluid imbalance.

The onset and progression of COPD is caused by an abnormal entry of ions into cells. The ions are moved through transporter proteins, or channels. Overactivation of one of these proteins, the epithelial sodium ion channel (ENaC), is involved in COPD development. Conversely, a genetic mutation of a chloride ion channel, the cystic fibrosis transmembrane conductance regulator (CFTR), causes CF.

Excessive production of mucus-producing genes (like MUC5AC) in the lungs is an important factor in the development of these diseases. However, scientists did not know why this occurs in COPD and CF.

So researchers investigated the ion channels ENaC and CFTR using human cystic fibrosis patient-derived cell lines and a mouse model of CF.

Results showed that abnormalities in the ENaC and CFTR ion channels induced a reduction of zinc transporters, causing a zinc deficiency in lung epithelial cells. This, in turn, activates MUC5AC, a mucin-producing protein.

The team also demonstrated that in COPD and CF, lung epithelial cells have abnormalities in splicing (editing) of messenger RNA (mRNA, the first product of the conversion of DNA into proteins), causing overproduction of mucous genes.

These findings establish a link between COPD and CF, the overproduction of mucus, and the insufficient supply of zinc to lung epithelial cells.

Overall, the study helps explain the involvement of zinc in the onset of pulmonary diseases, as well as its effects in mRNA regulation. The results also highlight that the importance of zinc in the lung goes far beyond nutrition.

The researchers emphasize that zinc supplements cannot simply be used by patients with these conditions, because an effective therapy needs to take into account the transport mechanisms of zinc ions.