LAUSR

ABSTRACT Chronic obstructive pulmonary disease (COPD) is regarded as a persistent respiratory symptom, mainly caused by cigarette smoking. Recent data have suggested that some miRNAs are involved in the pathogenesis of COPD. Here, we found that miR‐195 was significantly upregulated in the lung tissues of patients with COPD compared to in never smokers. miR‐195 expression was also upregulated in cigarette smoke (CS)‐exposed mice. Lentivirus‐mediated knockdown of miR‐195 alleviated CS‐induced lung pathological changes and reduced inflammatory cell infiltration as well as production of interleukin‐6 and tumor necrosis factor‐&agr; in bronchoalveolar lavage fluid. Mechanically, a positive correlation was found between miR‐195 and phosphorylation of Akt in lung tissues of COPD patients. PHLPP2 was confirmed as a direct downstream target of miR‐195 and negative regulator of miR‐195 expression. Inhibition of PHLPP2 enhanced Akt phosphorylation and increased interleukin‐6 and tumor necrosis factor‐&agr; production in BEAS‐2B cells, resembling the effects of miR‐195 overexpression. Collectively, our data indicate that miR‐195 has a pathogenetic role in CS‐induced COPD and regulates Akt signaling by suppressing PHLPP2 expression. miR‐195 may be an effective therapeutic target in COPD. HighlightsExpression of miR‐195 was increased in peripheral lung tissues from COPD patients.Inhibition of miR‐195 relieved CS‐induced lung injury and blocked the inflammatory processes in vivo.miR‐195 elevated Akt phosphorylation by suppressing PHLPP2 expression.PHLPP2 was involved in miR‐195–induced enhancement of Akt phosphorylation and cytokine production.