F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
Hepatic fibrosis (HF) is a precursor of liver cirrhosis, and activated hepatic stellate cells are an important driver of fibrosis. F-box and WD repeat domain containing 7 (FBXW7) expression level is down-regulated in HF, but the underlying mechanism is yet to be elucidated. The interaction between F...
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| Format: | Article |
| Language: | English |
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De Gruyter
2023-04-01
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| Series: | Open Medicine |
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| Online Access: | https://doi.org/10.1515/med-2023-0634 |
| _version_ | 1797832481796259840 |
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| author | Sun Yufeng He Lili Guo Peiran Li Fenghua Wang Bo Zhang Yifan An Kai Peng Ming |
| author_facet | Sun Yufeng He Lili Guo Peiran Li Fenghua Wang Bo Zhang Yifan An Kai Peng Ming |
| author_sort | Sun Yufeng |
| collection | DOAJ |
| description | Hepatic fibrosis (HF) is a precursor of liver cirrhosis, and activated hepatic stellate cells are an important driver of fibrosis. F-box and WD repeat domain containing 7 (FBXW7) expression level is down-regulated in HF, but the underlying mechanism is yet to be elucidated. The interaction between FBXW7 and delta-like ligand 1 (DLL1) was predicted. LX-2 cells were subjected to transfection of FBXW7/DLL1 silencing or overexpression plasmid. The expressions of FBXW7 and DLL1 in HF in vitro were measured by quantitative reverse transcription polymerase chain reaction and western blot. The LX-2 cell cycle, viability, proliferation, and ubiquitination were determined by flow cytometry, cell counting kit-8, colony formation, and ubiquitination assays, respectively. FBXW7 overexpression suppressed the cell viability and proliferation, facilitated cell cycle arrest, and down-regulated α-smooth muscle actin (α-SMA), Collagen I, and DLL1 protein levels, but FBXW7 silencing did the opposite. DLL1 was bound to and ubiquitin-dependently degraded by FBXW7 overexpression. DLL1 overexpression promoted the cell viability and proliferation, accelerated cell cycle, and up-regulated the levels of α-SMA, Collagen I, NOTCH2, NOTCH3, and HES1, but these trends were reversed by FBXW7 overexpression. To sum up, FBXW7 overexpression suppresses the progression of HF in vitro by ubiquitin-dependently degrading DLL1. |
| first_indexed | 2024-04-09T14:09:38Z |
| format | Article |
| id | doaj.art-421d177291174c8186b4de3595b35d89 |
| institution | Directory Open Access Journal |
| issn | 2391-5463 |
| language | English |
| last_indexed | 2024-04-09T14:09:38Z |
| publishDate | 2023-04-01 |
| publisher | De Gruyter |
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| series | Open Medicine |
| spelling | doaj.art-421d177291174c8186b4de3595b35d892023-05-06T15:31:53ZengDe GruyterOpen Medicine2391-54632023-04-01181e002226610.1515/med-2023-0634F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathwaySun Yufeng0He Lili1Guo Peiran2Li Fenghua3Wang Bo4Zhang Yifan5An Kai6Peng Ming7Department of Gastroenterology, The Second Hospital of Hebei Medical University, No. 215, West Heping Road, Shijiazhuang, Hebei, 050000, ChinaDepartment of Emergency, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei, ChinaCollege of Integrated Traditional Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Gastroenterology, The Second Hospital of Hebei Medical University, No. 215, West Heping Road, Shijiazhuang, Hebei, 050000, ChinaDepartment of Emergency, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Shijiazhuang First Hospital, Shijiazhuang, Hebei, ChinaDepartment of Rehabilitation, Shijiazhuang First Hospital, Shijiazhuang, Hebei, ChinaThe Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaHepatic fibrosis (HF) is a precursor of liver cirrhosis, and activated hepatic stellate cells are an important driver of fibrosis. F-box and WD repeat domain containing 7 (FBXW7) expression level is down-regulated in HF, but the underlying mechanism is yet to be elucidated. The interaction between FBXW7 and delta-like ligand 1 (DLL1) was predicted. LX-2 cells were subjected to transfection of FBXW7/DLL1 silencing or overexpression plasmid. The expressions of FBXW7 and DLL1 in HF in vitro were measured by quantitative reverse transcription polymerase chain reaction and western blot. The LX-2 cell cycle, viability, proliferation, and ubiquitination were determined by flow cytometry, cell counting kit-8, colony formation, and ubiquitination assays, respectively. FBXW7 overexpression suppressed the cell viability and proliferation, facilitated cell cycle arrest, and down-regulated α-smooth muscle actin (α-SMA), Collagen I, and DLL1 protein levels, but FBXW7 silencing did the opposite. DLL1 was bound to and ubiquitin-dependently degraded by FBXW7 overexpression. DLL1 overexpression promoted the cell viability and proliferation, accelerated cell cycle, and up-regulated the levels of α-SMA, Collagen I, NOTCH2, NOTCH3, and HES1, but these trends were reversed by FBXW7 overexpression. To sum up, FBXW7 overexpression suppresses the progression of HF in vitro by ubiquitin-dependently degrading DLL1.https://doi.org/10.1515/med-2023-0634hepatic fibrosislx-2 cellsdelta-like ligand 1ubiquitinationf-box and wd repeat domain containing 7 |
| spellingShingle | Sun Yufeng He Lili Guo Peiran Li Fenghua Wang Bo Zhang Yifan An Kai Peng Ming F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway Open Medicine hepatic fibrosis lx-2 cells delta-like ligand 1 ubiquitination f-box and wd repeat domain containing 7 |
| title | F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway |
| title_full | F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway |
| title_fullStr | F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway |
| title_full_unstemmed | F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway |
| title_short | F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway |
| title_sort | f box and wd repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta like ligand 1 to block notch signaling pathway |
| topic | hepatic fibrosis lx-2 cells delta-like ligand 1 ubiquitination f-box and wd repeat domain containing 7 |
| url | https://doi.org/10.1515/med-2023-0634 |
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