Involvement of epigenetic regulator lncRNA-HOTAIR in abnormal lung epithelial damage and repair in COPD
Involvement of epigenetic regulator lncRNA-HOTAIR in abnormal lung epithelial damage and repair in COPD
Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating lung disease that is caused by inhalation of noxious environmental factors, including cigarette smoking and air pollutants, in combination with genetic factors. These cause damage to the airway epithelial lining, leading to excessive mucus production, thickening of the airways, and destruction of the gas-exchange units (the alveoli), resulting in severe difficulties in breathing.
While the COPD triggers are known, the mechanisms underlying these pathological processes are less clear. Genetic factors cannot explain the susceptibility to COPD alone, and epigenetic processes have been implicated in COPD. Here, environmental factors change the expression of genes without changing the DNA sequence. One such epigenetic regulator is long non-coding RNA (lncRNA) HOTAIR, known to be increased by cigarette smoke and to induce airway epithelial abnormalities that have been associated with COPD. The study of Xinzi Zheng shows that cigarette smoke exposure upregulates HOTAIR expression in cultured airway epithelial cells from COPD patients, but not control subjects. The data suggest that elevated HOTAIR levels lead to higher binding to specific downstream molecules that contribute to the core airway epithelial pathological abnormalities of COPD. These include loss of epithelial barrier function, disruption of cells' mitochondrial function, exhaustion of tissue repair responses, and pro-inflammatory responses.
Finally, it may contribute to excessive airway epithelial mucus production that clogs airways. This research underscores the importance of dysregulated long non-coding RNAs in COPD, moving beyond the study of traditional protein-coding genes and opening new avenues towards treatment using epigenetic tools.