PTEN: An Emerging Potential Target for Therapeutic Intervention in Respiratory Diseases

Table 3

Biological functions of PTEN in the development of COPD.

Study type	Model/sample	Impact on PTEN	Additional signaling	Biological process	Ref.
In vivo/in vitro	Emphysema mouse model; bone marrow–derived macrophages (BMDMs); CSE-treated RAW264.7 and L929 cell lines	Decreased PTEN expression	Activated the PI3K/Akt pathway	Macrophage polarization toward the M2 phenotype in COPD	[75]
In vivo/in vitro	CS-exposed mouse model; BEAS-2B cells	Increased PTEN stability	Inhibited the PI3K/Akt pathway, decreased PRMT6 expression, promoted PI3Kp85 expression, and inhibited PDK1	Resulted in epithelial cell death in COPD	[76]
In vivo	Human lung tissue of COPD	Decreased PTEN expression	Activated HIF-1α signaling and MMP7/9	Decreased levels of oxidases (LOX, LOXL1, and LOXL2) caused abnormalities in elastic fiber biology	[77–79]
In vitro	CSE-exposed BEAS-2B cells	PTEN oxidation	Increased p-Akt level	Impaired Trx-1 activity	[80]
In vivo/in vitro	Lung tissues of patients with COPD; cells collected from patients undergoing lung resection surgery; BEAS-2B cells	Loss of PTEN expression	PI3K/mTOR signaling activation and SIRT1/6 inhibition	Caused cell senescence in COPD	[81, 82]
In vivo/in vitro	Human peripheral lung tissue; normal human bronchial epithelial cell line (16HEB)	Downregulation of PTEN	Decreased lncRNA SHNG5 sponge miR-132 expression	Regulated effects of CSE on cell proliferation, apoptosis, and inflammation	[84]
In vivo	Patients with COPD	Decreased PTEN expression	Enhanced the STAT3-AP-1 interaction	Increased MMP-9 expression to regulate airway remodeling	[87]
In vitro	Mouse cardiac endothelial cells (MCECs)	Low expression of PTEN	ROS/Src/EGFR-p38MAPK pathway	PTEN pathway related with AJC transcriptional reprograming to regulate epithelial barrier	[78, 90]
In vitro	Human nasal epithelial cell line (RPMI 2650)	Reduced PTEN activity	Increased TLR4/JNK/Bnip3 signaling	Activated mitophagy and induced mitochondrial dysfunction to cause epithelial cell apoptosis, proliferation arrest, and migration inhibition	[91]