Therapeutic efficacy of dexmedetomidine on chronic obstructive pulmonary disease via downregulating lncRNA PACER.

Abstract

The aim of the study was to clarify the therapeutic mechanism of Dexmedetomidine (DEX) on the chronic obstructive pulmonary disease (COPD) and its regulatory effect on long non-coding RNA (lncRNA) PACER. Serum level of PACER in COPD patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic potential of PACER in COPD was assessed by plotting ROC curves. The in vivo COPD model was generated in rats by cigarette smoking exposure. Primary rat alveolar epithelial cells were isolated, purified and cultured. After overexpression of PACER in primary rat alveolar epithelial cells, proliferative and migratory abilities were assessed by cell counting kit-8 (CCK-8) and transwell assay, respectively. Subsequently, we detected changes in PACER expression, viability and migratory potentials in primary rat alveolar epithelial cells harvested from control rats, and those harvested from COPD rats and induced with either DEX or not. Rescue experiments were conducted to uncover the involvement of PP2A in PACER-regulated cell phenotypes. PACER was upregulated in serum of COPD patients, which was a potential biomarker for diagnosing COPD. Overexpression of PACER in primary rat alveolar epithelial cells enhanced proliferative and migratory abilities. Compared with primary rat alveolar epithelial cells harvested from control rats, proliferative and migratory abilities were stronger in those harvested from COPD rats and induced with either DEX or not. Notably, DEX induction decreased PACER expression, and proliferative and migratory abilities in primary rat alveolar epithelial cells harvested from COPD rats. Overexpression of PP2A could partially abolish the promotive effects of PACER on proliferative and migratory abilities in DEX-induced primary rat alveolar epithelial cells harvested from COPD rats. PACER drives the proliferative and migratory abilities of alveolar epithelial cells through activating PP2A. Dexmedetomidine is conducive to COPD treatment by downregulating PACER.