Briefly, COPD model rats showed an increased basal release of inflammatory cytokines (lung TNF-α: 45.7 ± 6.1 vs. 20.1 ± 3.8 pg/mL, P < 0.01; serum TNF-α: 8.9 ± 1.2 vs. 6.7 ± 0.5 pg/mL, P = 0.01; lung TGF-β: 122.4 ± 20.8 vs. 81.9 ± 10.8 pg/mL, P < 0.01; serum TGF-β: 38.9 ± 8.5 vs. 20.6 ± 2.3 pg/mL, P < 0.01) and COPD related lung tissue histopathological changes, as well as corticosteroid resistance molecular profile characterized by an increase in phosphoinositide 3-kinase (PI3K)/Akt (0.5 ± 0.1 fold of control vs. 0.2 ± 0.1 fold of control, P = 0.04) and a decrease in HDAC2 expression and activity (expression: 13.1 ± 0.4 μmol/μg vs. 17.4 ± 1.1 μmol/μg, P < 0.01; activity: 1.1 ± 0.1 unit vs. 1.4 ± 0.1 unit, P < 0.01), compared with control group.
MicroRNA-34a (miR-34a), which is regulated by PI3K-mTOR signaling, plays a pivotal role in reducing sirtuin-1/6, and its inhibition with an antagomir results in their restoration, reducing markers of senescence, reducing senescence-associated secretory phenotype, and reversing cell cycle arrest in epithelial cells from peripheral airways of patients with COPD. miR-570 is also involved in reduction of sirtuin-1 and cellular senescence and is activated by p38 mitogen-activated protein kinase.
Here, we summarize the recent knowledge on the involvement of PI3K enzymes in the pathophysiology of COPD, and we discuss the most recent results arising from the preclinical as well as the clinical testing of PI3K inhibitors as novel therapeutics for COPD.
In conclusion, ECM proteins promoted proliferation, migration and adhesion of ASMCs form rat models of COPD through activation of the PI3K/AKT signaling pathway.
The aim of this study was to determine the expression and role of phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the PI3K pathway, in COPD.
This study compared the expression of PI3K isoforms by ASM cells from donors with asthma (A), chronic obstructive pulmonary disease (COPD), or neither disease (NA), and investigated the role of PI3K isoforms in the production of TGFβ1 induced pro-inflammatory cytokine and contractile proteins in ASM cells.
Surprisingly, the pro-survival neutrophil phenotype observed in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) was resilient to inactivation of the PI3K pathway.