Salidroside blocks the proliferation of pulmonary artery smooth muscle cells induced by platelet‑derived growth factor‑BB.
The proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the development of pulmonary vascular remodeling, ultimately leading to pulmonary hypertension. In this study, the effects and molecular mechanisms of salidroside on the platelet‑derived growth factor (PDGF)‑BB‑induced proliferation of primary cultured rat PASMCs were investigated. The presented data demonstrated that salidroside signiﬁcantly inhibited the proliferation and DNA synthesis of PASMCs induced by PDGF‑BB in a dose‑ and time‑dependent manner, without cell cytotoxicity. In accordance with these ﬁndings, salidroside blocked progression through G0/G1 to S phase of the cell cycle. The salidroside‑induced inhibition of the cell cycle was associated with the inhibition of cyclin D1, cyclin E, cyclin‑dependent kinase 2 (CDK2) and CDK4 mRNA expression, as well as an increase in the mRNA expression of p27 in PDGF‑BB‑stimulated PASMCs. Further experiments showed that the beneﬁcial effect of salidroside on blocking the proliferation of PASMCs was associated with the suppression of the AKT/glycogen synthase kinase 3 β (GSK3β) signaling pathway, but did not involve the extracellular signal‑regulated kinase 1/2, p38 and c‑Jun‑N‑terminal kinase signaling pathways. These results indicate that salidroside suppresses PDGF‑BB‑induced PASMC proliferation through the AKT/GSK3β signaling pathway and suggests that it may be a feasible therapy for pulmonary vascular remodeling diseases.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Changgui
C
Chen
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Yanhong
Y
Tang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Wei
W
Deng
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Congxin
C
Huang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Tianyi
T
Wu
D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D019927:Cyclin E; D005960:Glucosides; D010636:Phenols; D020574:Proto-Oncogene Proteins c-sis; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000077214:Becaplermin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D038362:Glycogen Synthase Kinase 3; C009172:rhodioloside