Effects of hesperetin on platelet-derived growth factor-BB-induced pulmonary artery smooth muscle cell proliferation

Wei,Li; Deng,Wei; Cheng,Zhihong; Guo,Haipeng; Wang,Shihong; Zhang,Xiao; He,Yiyu; Tang,Qizhu

doi:10.3892/mmr.2015.4625

Effects of hesperetin on platelet-derived growth factor-BB-induced pulmonary artery smooth muscle cell proliferation

Authors:
- Li Wei
- Wei Deng
- Zhihong Cheng
- Haipeng Guo
- Shihong Wang
- Xiao Zhang
- Yiyu He
- Qizhu Tang
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Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, National Pharmaceutical Engineering Research Center, Shanghai 201203, P.R. China, Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: November 30, 2015 https://doi.org/10.3892/mmr.2015.4625
Pages: 955-960

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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.

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