title: Effects of hesperetin on platelet-derived growth factor-BB-induced pulmonary artery smooth muscle cell proliferation.
abstract: Hesperetin is a natural flavonoid, which has been reported to exert various biological activities and positive health effects on mammalian cells. The present study aimed to investigate the effects of hesperetin on the proliferation of primary cultured rat pulmonary artery smooth muscle cells (PASMCs), and to elucidate the possible underlying molecular mechanisms. The results of the present study indicated that hesperetin was able to inhibit the proliferation and DNA synthesis of platelet‑derived growth factor‑BB (PDGF‑BB)‑induced PASMCs in a dose‑ and time‑dependent manner, without exerting cell cytotoxicity. In addition, hesperetin blocked the progression of the cell cycle from G0/G1 to S phase, which was correlated with the decreased mRNA expression levels of cyclin D1, cyclin E, cyclin‑dependent kinase (CDK)2 and CDK4, and the increased mRNA expression levels of p27. Furthermore, the anti‑proliferative effects of hesperetin were associated with suppression of the AKT/glycogen synthase kinase (GSK)3β and p38 signaling pathway, but were not associated with the extracellular signal‑regulated kinases 1/2 and c‑Jun N‑terminal kinases signaling pathways. These results suggested that hesperetin may inhibit PDGFa‑BB‑induced PASMC proliferation via the AKT/GSK3β signaling pathway, and that it may possess therapeutic potential for the treatment of pulmonary vascular remodeling diseases.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: National Pharmaceutical Engineering Research Center, Shanghai 201203, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Shihong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Qizhu
authors.initials: Q
authors.lastname: Tang
mesh_terms: D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006569:Hesperidin / Q000008:administration & dosage*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000235:genetics; D061251:Primary Cell Culture; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D006569:Hesperidin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3; C013015:hesperetin