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

Table 6

List of therapeutic drugs that modulate PTEN expression and activity in various lung diseases.

Diseases	Drug candidates	Models/samples	Effect on PTEN and target	Pharmacological effects	Ref.
Asthma	Resveratrol	Mouse/ovalbumin;16HBE cells	Restoration of PTEN expression and activation of SIRT1	Airway inflammation and airway remodeling	[132]
Asthma	Epigallo-catechin-3-gallate	Mouse/ovalbumin;16HBE cells/TGF-β1	Upregulation of PTEN and inhibition of PI3K/Akt	Suppresses inflammation and inflammatory cell infiltration; reduces airway remodeling by inhibiting EMT	[133]
Asthma	Borneol	Mouse/ovalbumin	Downregulation of miR-26a and miR-142-3p to upregulate PTEN expression	CD4+ T cell infiltration and proliferation	[134]
Asthma	α- and γ-mangostin	Mouse/ovalbumin	Upregulation of PTEN to suppress PI3K/Akt and NF-κB signaling	Reduces inflammatory cell recruitment into the airway, airway hyperresponsiveness (AHR), and increased levels of Th2 cytokines	[135]
Asthma	Korean red ginseng and Salvia plebeia R.Br.	Mouse/ovalbumin	Downregulation of phosphorylated PTEN and Akt and upregulation of PPAR-γ	Reduces the levels of Th2 cytokines IL-4, IL-5, and IL-13 in BALF and splenocytes and downregulates the IL-4, IL-13, IL-17, T-NF-α, and MUC5AC genes	[136]
Fibrosis	Dasatinib	Mice/bleomycin	Upregulation of PTEN and inhibition of PDGFR-alpha; Src and c-Abl activation	Myofibroblast activation and collagen-1 accumulation	[105]
Fibrosis	Unphosphorylated PTEN	H358 cells, fibroblast CC2512 cells and mouse primary lung fibroblasts/TGF-β1	Restores the loss of PTEN activity	Reduces fibronectin expression and ECM production	[118]
Fibrosis	Resveratrol	Normal and IPF-derived lung fibroblasts/TGF-β1	Upregulation of PTEN and downregulation of p-ERK and Akt	Inhibits cell proliferation of both normal and IPF-derived fibroblasts, α-SMA expression, and intracellular collagen deposition	[137]
Fibrosis	Prostaglandin E2	Primary normal fetal lung fibroblasts IMR-90	Increases PTEN activity and decreases p-Akt; downregulates survivin expression; increases Fas expression	Fibroblast apoptosis	[138]
Fibrosis	Berberine	Mice/bleomycin	Upregulation of PTEN in the colon; activation of PPAR-γ	Promotes HGF expression in colonic fibroblasts, which arrive in the lungs to palliate IPF	[139]
Fibrosis	Berberine	Wistar rats/bleomycin	Amplifies PTEN expression to inhibit FAK and PI3K/Akt/mTOR signaling; inhibits p-Smad 2/3 and enhances Smad 7 expression	Inhibits fibrotic markers, α-SMA, fibronectin, and collagens I and III and reverses bleomycin-induced ultrastructural alterations in the lungs	[140]
Inflammation	Coelonin	Raw264.7 cells/LPS	Upregulation of PTEN and inhibition of PTEN phosphorylation, resulting in suppressed NF-κB activation and p27^kip1 degradation	Cell-cycle arrest in the G1 phase	[141]
Acute pulmonary embolism	Curcumin	Sprague–Dawley rats	Downregulation of miR-21 expression via inhibition of Sp1 to upregulate PTEN and impair the NF-κB signaling pathway	Reduces mPAP and RVSP levels, W/D ratio, thrombus volume, and inflammatory factors	[143]
Pulmonary arterial hypertension	Cefminox	Primary rat pulmonary artery smooth muscle cells (PASMCs)/hypoxia	Upregulation of PTEN by inhibiting Akt/mTOR signaling and enhanced cAMP production	Inhibits growth of PASMCs as a dual agonist of prostacyclin receptor (IP) and PPAR-γ	[144]
Hypoxic pulmonary hypertension (HPH)	5-Aza-2-deoxycytidine	Sprague–Dawley rats/hypoxia; PASMCs/hypoxia	Rescues the decreased PTEN expression by inhibiting hypermethylation	Proliferation, migration, and induction of apoptosis in PASMCs; pulmonary artery pressure and right ventricular hypertrophy index in HPH	[146]
Lung injury	miR-486 mimic	A549/PM2.5	Negative regulation of PTEN and FOXO1	Reduces cell apoptosis and ROS generation	[147]
Lung injury by ischemia/reperfusion	miR-21-5p	Mice/(I/R); primary murine pulmonary endothelial cells/H/R	miR-21-5p targeting PTEN and PDCD4	Reduces lung edema and dysfunction, M1 polarization of alveolar macrophages, and secretion of proinflammatory cytokines	[148]
Lung injury	miR-371b-5p	A549 cells	Targets PTEN to inhibit phosphorylation of Akt and its downstream substrates, GSK3β and FOXOs	Augments ATIIC survival/proliferation, thereby promoting reepithelialization of injured alveoli	[149]
Chronic lung injury	Resveratrol	Mouse/methamphetamine	Activation of Sirt1 to downregulate PTEN and upregulation of p-Akt	Reduces oxidative stress and reverses MA-induced higher permeability and apoptosis of alveolar epithelium	[150]
Lung injury	Inhaled resveratrol	terc−/−F2 C57Bl/6J mice	Inactivates p-PTEN and activates p-Akt and p-Mdm2 via activation of SIRT1	Maintaining AECII integrity and prevent deterioration of lung function	[151]
Lung injury	Δ9 Tetrahydrocannabinol	C3H/HeJ mice/Staphylococcal enterotoxin B	Posttranscriptional upregulation of PTEN via inhibition of miR-18a	Prevents SEB-induced mortality and alleviates symptoms of toxic shock	[152]