Involvement of /PINK1-mediated mitophagy in chronic obstructive pulmonary disease induced by cigarette smoke or PM.

Background: This study sought to explore the underlying mechanism of long non-coding ribonucleic acid nuclear enriched abundant transcript 1 () and PTEN-induced kinase 1 (PINK1)-mediated mitophagy in chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS) or fine particular matter (PM).

Methods: In total, 30 male Wistar Rats were divided into the following 3 groups: (I) the COPD group exposed to CS (CSM); (II) the COPD group exposed to PM (PMM); and (III) the control (Ctrl) group. Pulmonary function, the enzyme-linked immunoassay analysis results, the histopathology results, and the ultrastructures of the lung tissues were examined in the 3 groups, and expression levels and the mitophagy-related protein PINK1, Parkin, LC3B, and p62 levels were assessed by quantitative reverse transcription PCR (RT-qPCR) and Western blotting. The A549 cells were transfected with small interfering ribonucleic acid (siRNA) targeting and subsequently stimulated with CS extract (CSE) and PM suspension (PMS). Mitochondrial dysfunction and enhanced mitophagy were observed, and the expression of the /PINK1 pathway was assessed by RT-qPCR and Western blotting.

Results: Both the CSM and PMM groups had a lower tidal volume (V), minute ventilation (MV), and a higher respiratory rate (f) than the Ctrl group. The interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha levels in the serum and bronchoalveolar lavage fluid of the CSM and PMM groups were significantly increased. The histological examination results revealed airway remodeling, the formation of pulmonary bullae, and emphysema in the CSM and PMM groups. Subsequently, the ultrastructures of the lung tissues in the CSM and PMM groups showed mitochondrial swelling and autophagosomes. Additionally, expression, the level of the mitophagy-related protein PINK1, Parkin, and the ratio of LC3-II/I increased synchronously. Further, siRNA blocked PINK1 expression, inhibited mitochondrial dysfunctions, and mitophagy activation in the A549 cells exposed to CSE or PMS.

Conclusions: Our results suggest that CS and PM exposure induce mitochondrial dysfunction, and the /PINK1 pathway plays a critical role in the occurrence and development of COPD by regulating mitophagy.