Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells <i>in vitro</i> by activating AMPK/mTOR-mediated autophagy
Restenosis is a pivotal factor that restricts the efficacy of coronary artery bypass grafting. Inhibition of vascular smooth muscle cells (VSMCs) proliferation can improve intimal hyperplasia and lumen stenosis. Irisin, a polypeptide secreted by muscle cells, has been demonstrated to have a protect...
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PAGEPress Publications
2024-10-01
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| Series: | European Journal of Histochemistry |
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| Online Access: | https://www.ejh.it/ejh/article/view/4104 |
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| author | Fenqiang Qi Yuxin Deng Wei Huang Yanli Cai Kelin Hong Shui Xiang |
| author_facet | Fenqiang Qi Yuxin Deng Wei Huang Yanli Cai Kelin Hong Shui Xiang |
| author_sort | Fenqiang Qi |
| collection | DOAJ |
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Restenosis is a pivotal factor that restricts the efficacy of coronary artery bypass grafting. Inhibition of vascular smooth muscle cells (VSMCs) proliferation can improve intimal hyperplasia and lumen stenosis. Irisin, a polypeptide secreted by muscle cells, has been demonstrated to have a protective role in various cardiovascular diseases. However, the effect and mechanism of irisin on VSMCs proliferation and phenotype switching remain unclear. Cell proliferation ability was assessed using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and 5-ethynyl-2'-deoxyuridine (EdU) incorporation. Cell cycle analysis was performed using flow cytometry, while expression levels of contractile and synthesis-related proteins were determined through RT-qPCR and Western blot. The VSMCs were infected with an adenovirus carrying GFP-LC3, and the proportion of cells showing positive expression was assessed. Additionally, the formation of autophagic lysosomes in cells was observed through transmission electron microscopy. In this study, we have demonstrated the inhibitory effects of irisin on the proliferation and phenotypic transition of platelet-derived growth factor-BB (PDGF-BB)-induced VSMCs. More importantly, we have discovered that irisin can activate the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway to mediate autophagy in PDGF-BB-induced VSMCs. The inhibitory effect of irisin on PDGF-BB-induced VSMCs proliferation was significantly attenuated by the AMPK inhibitor, Compound C. Conversely the mTOR inhibitor, rapamycin further enhanced the inhibitory effect of irisin on PDGF-BB induced VSMCs proliferation. In conclusion, our findings suggest that irisin effectively suppresses the aberrant proliferation of VSMCs following PDGF-BB stimulation by modulating autophagy levels through the AMPK/mTOR signaling pathway.
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| format | Article |
| id | doaj-art-7249dc26665e44fda35afbdd4726f1ab |
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| issn | 1121-760X 2038-8306 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | PAGEPress Publications |
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| series | European Journal of Histochemistry |
| spelling | doaj-art-7249dc26665e44fda35afbdd4726f1ab2025-08-20T01:47:37ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062024-10-0168410.4081/ejh.2024.4104Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells <i>in vitro</i> by activating AMPK/mTOR-mediated autophagyFenqiang Qi0Yuxin Deng1Wei Huang2Yanli Cai3Kelin Hong4Shui Xiang5Department of Cardiothoracic Surgery, Liuzhou Worker’s Hospital, LiuzhouDepartment of Cardiothoracic Surgery, Liuzhou Worker’s Hospital, LiuzhouDepartment of Cardiothoracic Surgery, Liuzhou Worker’s Hospital, LiuzhouDepartment of Cardiothoracic Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, EnshiDepartment of Cardiothoracic Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, EnshiDepartment of Cardiothoracic Surgery, Liuzhou Worker’s Hospital, Liuzhou; Department of Cardiothoracic Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi Restenosis is a pivotal factor that restricts the efficacy of coronary artery bypass grafting. Inhibition of vascular smooth muscle cells (VSMCs) proliferation can improve intimal hyperplasia and lumen stenosis. Irisin, a polypeptide secreted by muscle cells, has been demonstrated to have a protective role in various cardiovascular diseases. However, the effect and mechanism of irisin on VSMCs proliferation and phenotype switching remain unclear. Cell proliferation ability was assessed using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and 5-ethynyl-2'-deoxyuridine (EdU) incorporation. Cell cycle analysis was performed using flow cytometry, while expression levels of contractile and synthesis-related proteins were determined through RT-qPCR and Western blot. The VSMCs were infected with an adenovirus carrying GFP-LC3, and the proportion of cells showing positive expression was assessed. Additionally, the formation of autophagic lysosomes in cells was observed through transmission electron microscopy. In this study, we have demonstrated the inhibitory effects of irisin on the proliferation and phenotypic transition of platelet-derived growth factor-BB (PDGF-BB)-induced VSMCs. More importantly, we have discovered that irisin can activate the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway to mediate autophagy in PDGF-BB-induced VSMCs. The inhibitory effect of irisin on PDGF-BB-induced VSMCs proliferation was significantly attenuated by the AMPK inhibitor, Compound C. Conversely the mTOR inhibitor, rapamycin further enhanced the inhibitory effect of irisin on PDGF-BB induced VSMCs proliferation. In conclusion, our findings suggest that irisin effectively suppresses the aberrant proliferation of VSMCs following PDGF-BB stimulation by modulating autophagy levels through the AMPK/mTOR signaling pathway. https://www.ejh.it/ejh/article/view/4104Vascular smooth muscle cellsirisincell proliferationautophagyAMPK/mTOR signaling pathway |
| spellingShingle | Fenqiang Qi Yuxin Deng Wei Huang Yanli Cai Kelin Hong Shui Xiang Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells <i>in vitro</i> by activating AMPK/mTOR-mediated autophagy European Journal of Histochemistry Vascular smooth muscle cells irisin cell proliferation autophagy AMPK/mTOR signaling pathway |
| title | Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells <i>in vitro</i> by activating AMPK/mTOR-mediated autophagy |
| title_full | Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells <i>in vitro</i> by activating AMPK/mTOR-mediated autophagy |
| title_fullStr | Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells <i>in vitro</i> by activating AMPK/mTOR-mediated autophagy |
| title_full_unstemmed | Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells <i>in vitro</i> by activating AMPK/mTOR-mediated autophagy |
| title_short | Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells <i>in vitro</i> by activating AMPK/mTOR-mediated autophagy |
| title_sort | irisin suppresses pdgf bb induced proliferation of vascular smooth muscle cells i in vitro i by activating ampk mtor mediated autophagy |
| topic | Vascular smooth muscle cells irisin cell proliferation autophagy AMPK/mTOR signaling pathway |
| url | https://www.ejh.it/ejh/article/view/4104 |
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