Annals of translational medicine · 2023
Promotion of liver fibrosis by Y-box binding protein 1 via the attenuation of transforming growth factor-beta 3 transcription.
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Liao Qiong, Dong Yuwei, Li Binghang, Qin Jie, Cao Yangwei, Tu Wenjuan, Lu Lungen
Аннотация
BACKGROUND: Spurred by the seriousness of liver fibrosis, we evaluated the correlation between Y-box binding protein 1 (YB-1) and transforming growth factor-beta 3 (TGF-β3) expression levels in the signaling pathways of the disease.
METHODS: Based on a mouse model of carbon tetrachloride-induced liver fibrosis, YB-1 overexpression lentivirus was used to explore the effect of YB-1 on liver fibrosis in vivo. In addition, a hepatic stellate cell (HSC) activation model in the HSC line LX-2 was developed using TGF-β1. Western blot assays were used to investigate the effects of YB-1 overexpression and knockdown on liver fibrosis. Finally, chromatin immunoprecipitation and luciferase reporter assays were used to elucidate the relationship between YB-1 and its downstream signaling pathways.
RESULTS: YB-1 was overexpressed in fibrotic liver tissue, which enhanced both fibrosis and the relative protein expressions of the TGF-β pathway. Moreover, YB-1 overexpression promoted HSC activation in response to TGF-β1 stimulation, but its knockdown inhibited liver fibrosis in vitro. Both in vitro and in vivo experiments indicated the expression of TGF-β3 in the YB-1 overexpression group to be suppressed, and liver fibrosis was more obvious in the YB-1-overexpression group than in the YB-1-inhibition group. YB-1 attenuated TGF-β3 transcription by binding to its promoter, which is involved in the effect of YB-1 on liver fibrosis.
CONCLUSIONS: YB-1 overexpression in HSCs promoted liver fibrosis by attenuating TGF-β3 transcription.
METHODS: Based on a mouse model of carbon tetrachloride-induced liver fibrosis, YB-1 overexpression lentivirus was used to explore the effect of YB-1 on liver fibrosis in vivo. In addition, a hepatic stellate cell (HSC) activation model in the HSC line LX-2 was developed using TGF-β1. Western blot assays were used to investigate the effects of YB-1 overexpression and knockdown on liver fibrosis. Finally, chromatin immunoprecipitation and luciferase reporter assays were used to elucidate the relationship between YB-1 and its downstream signaling pathways.
RESULTS: YB-1 was overexpressed in fibrotic liver tissue, which enhanced both fibrosis and the relative protein expressions of the TGF-β pathway. Moreover, YB-1 overexpression promoted HSC activation in response to TGF-β1 stimulation, but its knockdown inhibited liver fibrosis in vitro. Both in vitro and in vivo experiments indicated the expression of TGF-β3 in the YB-1 overexpression group to be suppressed, and liver fibrosis was more obvious in the YB-1-overexpression group than in the YB-1-inhibition group. YB-1 attenuated TGF-β3 transcription by binding to its promoter, which is involved in the effect of YB-1 on liver fibrosis.
CONCLUSIONS: YB-1 overexpression in HSCs promoted liver fibrosis by attenuating TGF-β3 transcription.