Effects of bone morphogenetic protein 4 on TGF-β1-induced cell proliferation, apoptosis, activation and differentiation in mouse lung fibroblasts via ERK/p38 MAPK signaling pathway
©2022 Cai et al..
Fibroblasts, in particular myofibroblasts, are the critical effector cells in idiopathic pulmonary fibrosis (IPF), a deadly lung disease characterized by abnormal lung remodeling and the formation of "fibroblastic foci". Aberrant activation of TGF-β1 is frequently encountered and promotes fibroblast proliferation, activation, and differentiation in pulmonary fibrosis. Hence, the inhibition of TGF-β1-induced lung fibroblast activation holds promise as a therapeutic strategy for IPF. The present study aimed to investigate the potential effect and underlying mechanisms of bone morphogenetic protein 4 (BMP4) on TGF-β1-induced proliferation, apoptosis, activation and myofibroblast differentiation of adult lung fibroblasts. Here, we demonstrated that BMP4 expression was significantly decreased in TGF-β1-stimulated mouse primary lung fibroblasts (PLFs). BMP4 inhibited proliferation and apoptosis resistance of TGF-β1-stimulated mouse PLFs. BMP4 suppressed TGF-β1-induced fibroblast activation and differentiation in mouse PLFs. We also found that BMP4 inhibited TGF-β1-induced ERK and p38 MAPK phosphorylation. Our findings indicate that BMP4 exerts its anti-fibrotic effects by regulating fibroblast proliferation, apoptosis, activation and differentiation via the inhibition of the ERK/p38 MAPK signaling pathway, and thus has a potential for the treatment of pulmonary fibrosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
PeerJ - 10(2022) vom: 28., Seite e13775 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cai, Zhou [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.02.2023 Date Revised 14.02.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.7717/peerj.13775 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM344353702 |
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| 100 | 1 | |a Cai, Zhou |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of bone morphogenetic protein 4 on TGF-β1-induced cell proliferation, apoptosis, activation and differentiation in mouse lung fibroblasts via ERK/p38 MAPK signaling pathway |
| 264 | 1 | |c 2022 | |
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| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2022 Cai et al. | ||
| 520 | |a Fibroblasts, in particular myofibroblasts, are the critical effector cells in idiopathic pulmonary fibrosis (IPF), a deadly lung disease characterized by abnormal lung remodeling and the formation of "fibroblastic foci". Aberrant activation of TGF-β1 is frequently encountered and promotes fibroblast proliferation, activation, and differentiation in pulmonary fibrosis. Hence, the inhibition of TGF-β1-induced lung fibroblast activation holds promise as a therapeutic strategy for IPF. The present study aimed to investigate the potential effect and underlying mechanisms of bone morphogenetic protein 4 (BMP4) on TGF-β1-induced proliferation, apoptosis, activation and myofibroblast differentiation of adult lung fibroblasts. Here, we demonstrated that BMP4 expression was significantly decreased in TGF-β1-stimulated mouse primary lung fibroblasts (PLFs). BMP4 inhibited proliferation and apoptosis resistance of TGF-β1-stimulated mouse PLFs. BMP4 suppressed TGF-β1-induced fibroblast activation and differentiation in mouse PLFs. We also found that BMP4 inhibited TGF-β1-induced ERK and p38 MAPK phosphorylation. Our findings indicate that BMP4 exerts its anti-fibrotic effects by regulating fibroblast proliferation, apoptosis, activation and differentiation via the inhibition of the ERK/p38 MAPK signaling pathway, and thus has a potential for the treatment of pulmonary fibrosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Activation | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a BMP4 | |
| 650 | 4 | |a Fibroblasts | |
| 650 | 4 | |a Pulmonary fibrosis | |
| 650 | 4 | |a TGF-β1 | |
| 650 | 7 | |a Bone Morphogenetic Protein 4 |2 NLM | |
| 650 | 7 | |a p38 Mitogen-Activated Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.24 |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta1 |2 NLM | |
| 650 | 7 | |a Tgfb1 protein, mouse |2 NLM | |
| 650 | 7 | |a Bmp4 protein, mouse |2 NLM | |
| 700 | 1 | |a Guo, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yuanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, You |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Ran |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Xiaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Qiong |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Guoying |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Qiongqiong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Wenju |e verfasserin |4 aut | |
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