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

Table 1

Biological functions of PTEN in the development of asthma.

Study type	Model/sample	Impact on PTEN	Additional signaling	Biological process	Ref.
In vivo	Female BALB/c mice/OVA-induced	Decreased PTEN expression and activity	Activated PI3K signaling	Increased bronchial inflammation and airway hyperresponsiveness in asthma	[28]
In vivo	Female BALB/c mice/OVA-induced	PTEN expression increased by PPAR-γ	Reduced PI3K activity	Inhibited allergen-induced bronchial inflammation	[29]
In vivo	Female C57BL/6 mice	Inhibited PTEN expression	Activated HIF-α and VEGF signaling	Increased inflammation and vascular permeability	[30]
In vivo/in vitro	Female BALB/c mice/OVA-induced; A549 lung epithelial cell line	PTEN expression increased by dexamethasone treatment	Histone acetylation inhibition	Dexamethasone treatment upregulated PTEN and exhibited anti-inflammatory effect in asthma	[31]
In vivo	Female BALB/c mice/OVA-induced	Decreased PTEN expression		Promoted ASMC proliferation and airway tissue remodeling	[33]
In vitro	Human airway smooth muscle cells (ASMCs)	Overexpression of PTEN	Downregulated Akt and FAK signaling activity	Inhibited ASMC proliferation and migration	[34]
In vitro	Human ASMCs	Overexpression of PTEN	Downregulated Akt signaling and cyclin D1 expression, upregulated p21 expression	Inhibited ASMC proliferation and induced cell cycle arrest in the G0/G1 phase	[35]
In vivo/in vitro	Female BALB/c mice; mice Airway smooth muscle cells (ASMCs)/ TNF-α	Decreased PTEN expression	Increased CD38-mediated Ca^2+/CREB signaling	Promoted ASMC proliferation and airway tissue remodeling	[36]
In vitro	Mice airway smooth muscle cells (ASMCs)/TNF-α	Inhibited PTEN expression	Increased Notch1 expression	Facilitated ASMC proliferation and migration	[37]
In vivo/in vitro	Lung tissue specimens from asthma patients; bronchial smooth muscle (BSM) cells	Deregulated PTEN signaling	Increased miR-29a-3p and miR-92a-3p expression	Regulated cellular process in asthma	[38]
In vitro	Human ASMCs/HMGB1	Decreased PTEN expression	Activated the PI3K/Akt pathway and upregulated miR-19	Promoted ASMC proliferation and migration	[39]
In vitro	Human ASMCs/ TGF-β1	Decreased PTEN expression	Activated the PI3K/Akt pathway and upregulated miR-19	Induced ASMC proliferation and inhibited apoptosis	[40]
In vitro	Mice airway smooth muscle cells (ASMCs)/TGF-β1	Decreased PTEN expression	Upregulated miR-181a and activated the Akt/mTOR pathway	Promoted airway smooth muscle cell proliferation and airway remodeling	[41]
In vitro	Human ASMCs/miR-21 lentiviral vector	Decreased PTEN expression	Activated the PI3K/Akt pathway and upregulated miR-21	Promoted ASMC proliferation and migration	[42]
In vivo	Murine model of established allergic airway disease (AAD)	Inhibited PTEN expression	High levels of miR-21 enhanced the PI3K/Akt pathway and suppressed nuclear histone deacetylase (HDAC2)2 levels	Induced airway hyperresponsiveness in severe, steroid-insensitive asthma	[43]
In vivo/in vitro	Female BALB/c mice; P815 cells	Suppressed PTEN expression	Increased miR-221 activated p38 and NF-κB signaling	Stimulated IL-4 secretion in mast cells	[44]
In vivo/in vitro	Human bronchial biopsies from asthma patients; human ASMCs	Downregulated PTEN expression	Activated STAT3 and miR-21-5p	Induced ASMC remodeling	[45]
In vitro	Human ASMCs	Suppressed PTEN expression	LncRNA-CASC7 levels were suppressed, and miR-21 levels were increased; the PI3K/Akt pathway was activated	Enhanced corticosteroid sensitivity in severe asthma	[46]
In vivo/in vitro	Serum samples from asthma patients; human ASMCs	Suppressed PTEN expression	LncRNA-H19 levels were suppressed, and miR-21 levels were increased; the PI3K/Akt pathway activated	Promoted ASMC proliferation and migration	[47]
In vitro	Human bronchial epithelial cell line (BEAS-2B)	PTEN expression was repressed by Bap treatment	Repressed FAK expression and activated the PI3K/Akt pathway	Induced bronchial epithelial cell apoptosis and cell injury	[48]