PDK1 inhibition reduces autophagy and cell senescence through the PI3K/AKT signalling pathway in a cigarette smoke mouse emphysema model

Zhang,Peibei; Jiang,Youjun; Ye,Xianwei; Zhang,Cheng; Tang,Yiling

doi:10.3892/etm.2023.11922

PDK1 inhibition reduces autophagy and cell senescence through the PI3K/AKT signalling pathway in a cigarette smoke mouse emphysema model

Authors:
- Peibei Zhang
- Youjun Jiang
- Xianwei Ye
- Cheng Zhang
- Yiling Tang
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Affiliations: Department of Respiratory Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China
Published online on: March 30, 2023 https://doi.org/10.3892/etm.2023.11922
Article Number: 223

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Abstract

A number of previous studies have demonstrated the pivotal role of PI3K/AKT signalling in cigarette smoke (CS)‑induced emphysema, where phosphoinositide dependent protein kinase 1 (PDK1) is a critical component of this pathway. Therefore, the present study aimed to investigate the effects of a PDK1 inhibitor (GSK‑2334470) on the expression levels of PI3K, AKT, cyclin‑dependent kinase inhibitor 2A (p16) and LC3B in a CS + CS extract (CSE)‑induced mouse emphysema model. CS exposure and intraperitoneal injections of CSE were combined for 4 weeks to establish an emphysema model. Mice (n=35) were randomly divided into the normal control, emphysema (CS), PI3K inhibitor (CS3) and PDK1 inhibitor (CS1) groups. Immunohistochemistry staining of lung tissues was used to measure the expression of the PI3K, PDK1 and AKT proteins in airway epithelial tissues. Immunofluorescence staining was also used to measure the levels of p16 and LC3BII protein expression in the airway epithelial tissues. In addition, PI3K, PDK1, AKT, p16 and LC3B protein expression was semi‑quantified using western blotting. The expression of PDK1, PI3K and AKT proteins in the airway epithelial tissues was significantly increased in the CS + CSE group compared with that in the control group. The expression levels of p16 and LC3B were also increased as well in the CS + CSE group compared with those in the control group. The expression levels of PI3K, PDK1, AKT, LC3B and p16 in the airway epithelial tissues of the CS3 group were lower compared with those in the CS + CSE group. A decrease in the expression levels of PDK1, AKT, p16 and LC3B in the airway epithelial tissues of the CS1 group compared with those in the CS + CSE group was also observed. However, there were no significant differences in the expression levels of PI3K between the CS1 and the CS groups. The present study concluded that the inhibition of PDK1 can potentially reduce autophagy and cell senescence by downregulating the expression of PI3K/AKT pathway related proteins in airway epithelial cells, thereby protecting against CS + CSE‑induced emphysema in mice.

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