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

Table 5

Biological function of PTEN in the development of PAH.

Study type	Model/sample	Impact on PTEN	Additional signaling	Biological process	Ref.
In vivo/in vitro	SD Rat/monocrotaline; human PASMCs/hypoxia	Low levels of PTEN	High expression of miR-132	Increased proliferation and migration of PASMCs	[119]
In vitro	Human PASMCs/hypoxia	Reduction of PTEN expression	High expression of miR-17-5p; down-regulation of p21	Aberrant proliferation and migration of PASMCs	[120]
In vivo/in vitro	SD rats/ monocrotaline; pulmonary arterial endothelial cells/MCT	Increases of PTEN expression	Downregulation of miR-371b-5p	Increased endothelial apoptosis	[121]
In vivo/in vitro	SD rats/monocrotaline, hypoxia; human PASMCs/hypoxia	Low expression of PTEN and reduced p-PTEN levels due to ubiquitination	Akt phosphorylation and inactivation of p53, p21, and p27	Increased proliferation of PASMCs	[122]
In vivo	Male SD rats/ monocrotaline, hypoxia	Low expression of PTEN due to its ubiquitination	Aberrant activation of PI3K/Akt signaling	Enhanced vascular remodeling	[123]
In vivo	Human PAH lung; PASMCs male SD rats/monocrotaline	Low levels of PTEN due to decreased p-CREB expression	PGE1 induced pCREB expression	Vascular remodeling and improved hemodynamics	[124]
In vivo/in vitro	Mice/hypoxia; human PASMCs/hypoxia	Decreased expression of PTEN	miR-19a overexpression enhanced PI3K/Akt signaling	Increased proliferation and migration of PASMCs	[126]
In vitro	Human PASMCs/hypoxia	Decreased expression of PTEN	Downregulation of lncRNA MEG3; over-expression of miR-21	Increased proliferation and migration of PASMCs	[127]
In vivo/in vitro	Human HAP; male SD rats/hypoxia	Decreased phosphatase activity or deletion of PTEN	Increased Akt phosphorylation	Increased pressure, extensive, pulmonary vascular remodeling, and increased macrophage accumulation	[128]
In vivo /in vitro	Adult female/male Wistar rats/hypoxia; human PASMCs/hypoxia	Low expression of PTEN	Activation of PI3K/Akt signaling	PASMCs resistant to apoptosis	[129]
In vivo/in vitro	Male SD rats/permanent ligation of left anterior descending; human PASMCs/hypoxia	Downregulation and decreased phosphatase activity of PTEN	Phosphorylation of Akt	Enhanced proliferative, vascular remodeling	[130]