LOXL1 Protein Levels Elevated in Airways of COPD Patients, Smokers
Levels of a protein called LOXL1 are elevated in the lungs of people who smoke cigarettes, as well as in those with chronic obstructive pulmonary disease (COPD), a recent study reported.
According to researchers, these findings highlight the importance of LOXL1 and similar proteins in disease processes associated with smoking and their potential as new treatment targets for COPD.
The study, “Differential roles for lysyl oxidase (like), family members in chronic obstructive pulmonary disease; from gene and protein expression to function,” was published in The FASEB Journal.
Lysyl oxidases, or LOs, are a family of enzymes that are important for controlling the arrangement of collagens — the main structural proteins in the body. By regulating how different collagens are interwoven, LOs can have profound effects on the stiffness or stretchiness of tissues.
LOXL1 levels higher in outer layer of small airways
Prior research has shown that some LOs are dysregulated in lung diseases like idiopathic pulmonary fibrosis (IPF), which causes scar tissue to gradually buildup in the lungs. However, this enzyme family has not been thoroughly studied in COPD, and little is known about how exposure to cigarette smoke — a known risk factor for COPD and other lung diseases — affects LOs.
A team led by researchers in the Netherlands conducted a series of experiments to learn more.
“This study is the first to explore the role of the LOs family members in relation to presence and severity of COPD and smoking status,” the scientists wrote.
The team first conducted analyses of gene expression data from a public database. This type of data can be used to evaluate which genes are “turned on” or “off” in specific tissues under particular circumstances. Analysis included data from 87 current and ex-smoking COPD patients, as well as from 151 current and former smokers without COPD.
Results showed that a LO gene called LOXL1 was expressed at increased levels in COPD patients, and that higher LOXL1 expression was statistically associated with poorer lung function. Expression of another LO gene, called LOX, was elevated in current smokers compared with ex-smokers.
Scientists then analyzed samples of lung tissue from 64 people — 31 COPD patients, and 33 people without COPD who were a mix of current, former, and never-smokers serving as controls. Among controls, smokers had higher levels of the LO proteins LOXL1 and LOXL2 throughout the lungs.
Several differences in LO protein levels were noted between COPD patients and controls, though patterns varied depending on the region of the lung and the specific LO protein. Notably, LOXL1 levels were higher in the outer layer of the small airways of COPD patients compared with controls.
“The LO family of enzymes is often considered as a whole; however, each of the family members has individual, occasionally opposite, functions … our findings indicate differential regulation of LO family members in the airways of current smokers and COPD patients, with LOXL1 being the only member showing consistent higher levels with both smoking and COPD,” the researchers wrote.
This association implies LOXL1 may have disease-associated activity in COPD, they added.
Experiments using mouse lung tissue treated with a chemical that powerfully inhibits LO activity found that blocking this enzyme family markedly decreased the stiffness of lung tissue and improved airway contraction.
These results generally support the idea that increased activity of some LOs could contribute to disease progression in COPD, though researchers noted that the specific blocking chemical used is too toxic for clinical application.
About the Author
