title: Role of the PI3K/AKT pathway in modulating cytoskeleton rearrangements and phenotype switching in rat pulmonary arterial vascular smooth muscle cells.
abstract: Pulmonary arterial smooth muscle cell (PASMC) phenotype switching, which is characterized by changes in smooth muscle (SM)-specific gene expression, contributes to vascular remodeling in pulmonary hypertension. In addition, it has been shown that the transcription of SM-specific genes is modulated by cytoskeleton rearrangement. However, the intracellular mechanisms and signaling pathways that regulate these relationships are largely unknown. In the present study, we aimed to investigate the roles that phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB), also known as AKT, play in modulating the cytoskeleton and phenotype of rat PASMCs. To observe the downstream effects of inhibiting or enhancing PI3K/AKT pathway activity, we used various approaches to manipulate protein function and gene expression. Treatment of PASMCs with platelet-derived growth factor (PDGF)-BB or PIK3CA-adenovirus induced cytoskeleton rearrangements and downregulated SM22α and α-SM actin gene expression. Inhibition of PI3K led to blocking of AKT phosphorylation and attenuated the PDGF-BB-induced downregulation of F-actin and SM-specific genes, the downstream effector of PI3K. The decrease in SM22α and α-SM actin mRNA levels induced by PDGF-BB was markedly and reproducibly blocked by LY294002. PI3K/AKT pathway plays a vital role in the modulation of PASMCs cytoskeleton rearrangement and phenotype switching.
authors.affiliation: 1 Pulmonary Vascular Remodeling Research Unit, West China Institute of Women's and Children's Health, West China Second University Hospital, Sichuan University , Chengdu, China .
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Fan
authors.forename: Chunyu
authors.initials: C
authors.lastname: Li
authors.forename: Chaoyi
authors.initials: C
authors.lastname: Qin
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Wang
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Gao
authors.lastname: Qiangbacuozhen
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Hanmin
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003599:Cytoskeleton / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt