Intermittent hypoxia induces myofibroblast differentiation and extracellular matrix production of MRC5s via HIF-1α-TGF-β/Smad pathway
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG..
PURPOSE: To investigate whether or not intermittent hypoxia (IH), the main characteristic of obstructive sleep apnea (OSA) may affect the myofibroblast differentiation and extracellular matrix (ECM) production of lung fibroblast through the HIF-1α-TGF-β/Smad pathway and assess the interventional role of a HIF-1α inhibitor, 2-methoxyestradiol (2-ME2).
METHOD: The human lung fibroblast MRC5 cells were exposed to normoxia or IH conditions, and the expression of myofibroblast differentiation marker α-smooth muscle actin (α-SMA) and ECM protein collagen I were evaluated. To clarify the underlying mechanism, the expression level of HIF-1α, TGF-β, and p-Smads/Smads were measured and the effects of inhibiting HIF-1α with 2-ME2 on the α-SMA expression level and ECM production through the TGF-β/Smad pathway were assessed. Si HIF-1α was applied to genetically inhibit HIF-1α in MRC5 cells, and the related proteins were assessed.
RESULTS: IH increased the protein and mRNA expression of Collagen I and α-SMA of MRC5 cells in a time-dependent manner. IH activated the protein and mRNA level of HIF-1α and TGF-β and increased the phosphorylation of Smad2/Smad3 of MRC5 cells in a time-dependent manner. 2-ME2 inhibited the activation of HIF-1α induced by IH and decreased overexpression of TGF-β, p-Smad2/Smad2, and p-Smad3/Smad3, which in turn partially reversed the upregulation of α-SMA and Collagen I induced by IH in MRC5 cells. When HIF-1α was successfully silenced by si-HIF-1α, upregulation of TGF-β induced by intermittent hypoxia was partially decreased.
CONCLUSIONS: This study showed that IH contributes to myofibroblast differentiation and excessive ECM production of MRC5 cells through activation of the HIF-1α-TGF-β/Smad pathway. 2-ME2 partially attenuated myofibroblast differentiation induced by IH by inhibiting the HIF-1α-TGF-β/Smad pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Sleep & breathing = Schlaf & Atmung - 28(2024), 1 vom: 29. März, Seite 291-300 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liang, Maoli [VerfasserIn] |
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| Links: |
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| Themen: |
9007-34-5 |
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| Anmerkungen: |
Date Completed 21.03.2024 Date Revised 21.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s11325-023-02889-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361961243 |
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| 100 | 1 | |a Liang, Maoli |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intermittent hypoxia induces myofibroblast differentiation and extracellular matrix production of MRC5s via HIF-1α-TGF-β/Smad pathway |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 21.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG. | ||
| 520 | |a PURPOSE: To investigate whether or not intermittent hypoxia (IH), the main characteristic of obstructive sleep apnea (OSA) may affect the myofibroblast differentiation and extracellular matrix (ECM) production of lung fibroblast through the HIF-1α-TGF-β/Smad pathway and assess the interventional role of a HIF-1α inhibitor, 2-methoxyestradiol (2-ME2) | ||
| 520 | |a METHOD: The human lung fibroblast MRC5 cells were exposed to normoxia or IH conditions, and the expression of myofibroblast differentiation marker α-smooth muscle actin (α-SMA) and ECM protein collagen I were evaluated. To clarify the underlying mechanism, the expression level of HIF-1α, TGF-β, and p-Smads/Smads were measured and the effects of inhibiting HIF-1α with 2-ME2 on the α-SMA expression level and ECM production through the TGF-β/Smad pathway were assessed. Si HIF-1α was applied to genetically inhibit HIF-1α in MRC5 cells, and the related proteins were assessed | ||
| 520 | |a RESULTS: IH increased the protein and mRNA expression of Collagen I and α-SMA of MRC5 cells in a time-dependent manner. IH activated the protein and mRNA level of HIF-1α and TGF-β and increased the phosphorylation of Smad2/Smad3 of MRC5 cells in a time-dependent manner. 2-ME2 inhibited the activation of HIF-1α induced by IH and decreased overexpression of TGF-β, p-Smad2/Smad2, and p-Smad3/Smad3, which in turn partially reversed the upregulation of α-SMA and Collagen I induced by IH in MRC5 cells. When HIF-1α was successfully silenced by si-HIF-1α, upregulation of TGF-β induced by intermittent hypoxia was partially decreased | ||
| 520 | |a CONCLUSIONS: This study showed that IH contributes to myofibroblast differentiation and excessive ECM production of MRC5 cells through activation of the HIF-1α-TGF-β/Smad pathway. 2-ME2 partially attenuated myofibroblast differentiation induced by IH by inhibiting the HIF-1α-TGF-β/Smad pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ECM production | |
| 650 | 4 | |a HIF-1α-TGF-β/Smad pathway | |
| 650 | 4 | |a Intermittent hypoxia | |
| 650 | 4 | |a Myofibroblast differentiation | |
| 650 | 4 | |a Obstructive sleep apnea | |
| 650 | 7 | |a Collagen |2 NLM | |
| 650 | 7 | |a 9007-34-5 |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 700 | 1 | |a Si, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Le |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Baoyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Jie |e verfasserin |4 aut | |
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