NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
This study aimed to examine whether nuclear receptor 4a1 (NR4A1) is involved in inhibiting hepatic stellate cell (HSC) activation and liver fibrosis through the epithelial–mesenchymal transition (EMT). HSC-T6 cells were divided into the control group, the acetaldehyde (200 μM, an EMT activator) grou...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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De Gruyter
2022-05-01
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| Series: | Open Life Sciences |
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| Online Access: | https://doi.org/10.1515/biol-2022-0047 |
| _version_ | 1828383461443895296 |
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| author | Huang Qian Xu Jingying Ge Yanyan Shi Yue Wang Fei Zhu Mingli |
| author_facet | Huang Qian Xu Jingying Ge Yanyan Shi Yue Wang Fei Zhu Mingli |
| author_sort | Huang Qian |
| collection | DOAJ |
| description | This study aimed to examine whether nuclear receptor 4a1 (NR4A1) is involved in inhibiting hepatic stellate cell (HSC) activation and liver fibrosis through the epithelial–mesenchymal transition (EMT). HSC-T6 cells were divided into the control group, the acetaldehyde (200 μM, an EMT activator) group, and the NR4A1 activation group (Cytosporone B; 1 μM). The expression levels of the epithelial marker E-cadherin, the mesenchymal markers fibronectin (FN), vimentin, smooth muscle alpha-actin (α-SMA), and fibroblast-specific protein 1 (FSP-1), and the components of the transforming growth factor (TGF)-β pathway were detected by real-time polymerase chain reaction and western blotting. Compared with the control group, E-cadherin in the acetaldehyde group was downregulated, whereas FN, FSP-1, vimentin, α-SMA, and COL1A1/COL1A2 were upregulated (P < 0.05). Compared with the acetaldehyde group, NR4A1 agonist upregulated E-cadherin and downregulated FN, FSP-1, vimentin, α-SMA, and COL1A1/COL1A2 (P < 0.05). After acetaldehyde stimulation, TGF-β, Smad2/3/4, and zinc finger E-box-binding homeobox (ZEB) were upregulated, while Smad7 mRNA levels were downregulated (all P < 0.05). Compared with acetaldehyde alone, NR4A1 agonist increased Smad7 mRNA levels and reduced TGF-β, Smad2/3/4, and ZEB mRNA levels (all P < 0.05). NR4A1 activation suppresses acetaldehyde-induced EMT, as shown by epithelial and mesenchymal marker expression. The inhibition of the TGF-β–Smad2/3/4–ZEB signaling during HSC activation might be involved. |
| first_indexed | 2024-12-10T04:49:33Z |
| format | Article |
| id | doaj.art-ff0704c838c1448db124c03b18d48fa3 |
| institution | Directory Open Access Journal |
| issn | 2391-5412 |
| language | English |
| last_indexed | 2024-12-10T04:49:33Z |
| publishDate | 2022-05-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Life Sciences |
| spelling | doaj.art-ff0704c838c1448db124c03b18d48fa32022-12-22T02:01:40ZengDe GruyterOpen Life Sciences2391-54122022-05-0117144745410.1515/biol-2022-0047NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signalingHuang Qian0Xu Jingying1Ge Yanyan2Shi Yue3Wang Fei4Zhu Mingli5Department of Infectious Diseases, Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, 310023, ChinaDepartment of Infectious Diseases, Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, 310023, ChinaDepartment of Internal Medicine, Hangzhou Third People’s Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, 310009, ChinaDepartment of Infectious Diseases, Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, 310023, ChinaDepartment of Infectious Diseases, Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, 310023, ChinaDepartment of Laboratory Medicine, Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, 310023, ChinaThis study aimed to examine whether nuclear receptor 4a1 (NR4A1) is involved in inhibiting hepatic stellate cell (HSC) activation and liver fibrosis through the epithelial–mesenchymal transition (EMT). HSC-T6 cells were divided into the control group, the acetaldehyde (200 μM, an EMT activator) group, and the NR4A1 activation group (Cytosporone B; 1 μM). The expression levels of the epithelial marker E-cadherin, the mesenchymal markers fibronectin (FN), vimentin, smooth muscle alpha-actin (α-SMA), and fibroblast-specific protein 1 (FSP-1), and the components of the transforming growth factor (TGF)-β pathway were detected by real-time polymerase chain reaction and western blotting. Compared with the control group, E-cadherin in the acetaldehyde group was downregulated, whereas FN, FSP-1, vimentin, α-SMA, and COL1A1/COL1A2 were upregulated (P < 0.05). Compared with the acetaldehyde group, NR4A1 agonist upregulated E-cadherin and downregulated FN, FSP-1, vimentin, α-SMA, and COL1A1/COL1A2 (P < 0.05). After acetaldehyde stimulation, TGF-β, Smad2/3/4, and zinc finger E-box-binding homeobox (ZEB) were upregulated, while Smad7 mRNA levels were downregulated (all P < 0.05). Compared with acetaldehyde alone, NR4A1 agonist increased Smad7 mRNA levels and reduced TGF-β, Smad2/3/4, and ZEB mRNA levels (all P < 0.05). NR4A1 activation suppresses acetaldehyde-induced EMT, as shown by epithelial and mesenchymal marker expression. The inhibition of the TGF-β–Smad2/3/4–ZEB signaling during HSC activation might be involved.https://doi.org/10.1515/biol-2022-0047liver fibrosisnuclear receptor 4a1epithelial–mesenchymal transition |
| spellingShingle | Huang Qian Xu Jingying Ge Yanyan Shi Yue Wang Fei Zhu Mingli NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling Open Life Sciences liver fibrosis nuclear receptor 4a1 epithelial–mesenchymal transition |
| title | NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling |
| title_full | NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling |
| title_fullStr | NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling |
| title_full_unstemmed | NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling |
| title_short | NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling |
| title_sort | nr4a1 inhibits the epithelial mesenchymal transition of hepatic stellate cells involvement of tgf β smad2 3 4 zeb signaling |
| topic | liver fibrosis nuclear receptor 4a1 epithelial–mesenchymal transition |
| url | https://doi.org/10.1515/biol-2022-0047 |
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