NAMPT mediates PDGF-induced pulmonary arterial smooth muscle cell proliferation by TLR4/NF-κB/PLK4 signaling pathway
Copyright © 2023 Elsevier B.V. All rights reserved..
Nicotinamide phosphoribosyltransferase (NAMPT), a pleiotropic protein, promotes the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), which is associated with the genesis and progression of pulmonary arterial hypertension (PAH). NAMPT is highly increased in PAH patient's plasma and highly relevant to PAH severity. The mRNA and protein levels of NAMPT are elevated in PAH animal models. However, the underlying molecular mechanisms how NAMPT mediated platelet-derived growth factor (PDGF)-induced PASMCs proliferation are still unclear. The present study aimed to address these issues. Primary cultured PASMCs were attained from male Sprague-Dawley (SD) rats. Western blotting, RT-PCR, ELISA, cell transfection, Cell Counting Kit-8 (CCK-8) and EdU incorporation assays were used in the experiments. We showed that PDGF upregulated NAMPT expression through the activation of signal transducers and activators of transcription 5 (STAT5), and elevated extracellular NAMPT further promoted the activation of NF-κB through Toll-like receptor 4 (TLR4), which ultimately upregulated polo-like kinase 4 (PLK4) expression leading to PASMCs proliferation. Knockdown of STAT5, NAMPT or PLK4, and inhibition of TLR4 or NF-κB suppressed PDGF-induced PASMCs proliferation. Our study suggests that NAMPT plays an essential role in PDGF-induced PASMCs proliferation via TLR4/NF-κB/PLK4 pathway, suggesting that targeting NAMPT might be valuable in ameliorating pulmonary arterial hypertension.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:961 |
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| Enthalten in: |
European journal of pharmacology - 961(2023) vom: 15. Dez., Seite 176151 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Danyang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 16.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejphar.2023.176151 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364059583 |
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| 520 | |a Nicotinamide phosphoribosyltransferase (NAMPT), a pleiotropic protein, promotes the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), which is associated with the genesis and progression of pulmonary arterial hypertension (PAH). NAMPT is highly increased in PAH patient's plasma and highly relevant to PAH severity. The mRNA and protein levels of NAMPT are elevated in PAH animal models. However, the underlying molecular mechanisms how NAMPT mediated platelet-derived growth factor (PDGF)-induced PASMCs proliferation are still unclear. The present study aimed to address these issues. Primary cultured PASMCs were attained from male Sprague-Dawley (SD) rats. Western blotting, RT-PCR, ELISA, cell transfection, Cell Counting Kit-8 (CCK-8) and EdU incorporation assays were used in the experiments. We showed that PDGF upregulated NAMPT expression through the activation of signal transducers and activators of transcription 5 (STAT5), and elevated extracellular NAMPT further promoted the activation of NF-κB through Toll-like receptor 4 (TLR4), which ultimately upregulated polo-like kinase 4 (PLK4) expression leading to PASMCs proliferation. Knockdown of STAT5, NAMPT or PLK4, and inhibition of TLR4 or NF-κB suppressed PDGF-induced PASMCs proliferation. Our study suggests that NAMPT plays an essential role in PDGF-induced PASMCs proliferation via TLR4/NF-κB/PLK4 pathway, suggesting that targeting NAMPT might be valuable in ameliorating pulmonary arterial hypertension | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a NAMPT | |
| 650 | 4 | |a PLK4 | |
| 650 | 4 | |a Pulmonary arterial hypertension | |
| 650 | 4 | |a Pulmonary artery smooth muscle cells | |
| 650 | 7 | |a Platelet-Derived Growth Factor |2 NLM | |
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| 650 | 7 | |a Nicotinamide Phosphoribosyltransferase |2 NLM | |
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| 700 | 1 | |a Chen, Yuqian |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Chai, Limin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qianqian |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Yuanjie |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Nirui |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xiangyu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Manxiang |e verfasserin |4 aut | |
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