2018
DOI: 10.1096/fj.201701137r
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Inhibition of GSK‐3β induces AP‐1‐mediated osteopontin expression to promote cholestatic liver fibrosis

Abstract: The contribution of glycogen synthase kinase-3β (GSK-3β) to cholestatic liver disease (CLD) remains unknown. We investigated the role and mechanism of GSK-3β in vivo in liver tissues of patients with CLD and the bile duct ligation (BDL) mouse model and in vitro using a hepatic progenitor cell (HPC) and hepatic stellate cell (HSC) coculture system. In liver tissues of patients with CLD, expression of the inactive form of GSK-3β, phospho-GSK-3β(Ser9), was increased in HPCs. GSK-3β inhibition by SB216763 treatmen… Show more

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Cited by 20 publications
(11 citation statements)
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“…Aside from melanoma, AP-1/ TEADs modulates the expression of a core set of genes involved in migration and invasion of different types of cancer cells, including neuroblastoma, colorectal cancer, and lung cancer (Liu et al, 2016). Regarding the AP-1 transcriptional targets, it is worth noting that melanoma cells failing to die upregulate Cell Reports 31, 107731, June 9, 2020 11 Article ll OPEN ACCESS several genes, such as PTX3, MYLK, SPP1, and RAC2, all shown to be regulated by AP-1 and involved in metastasis (Zhang et al, 2015;Khapchaev and Shirinsky, 2016;Zhuang et al, 2018;Hartl et al, 2006). Although, in these studies, the AP-1/c-JUN transcription factors are activated by a plethora of stimuli, such as cytokines, growth factors, UV irradiation, or activating mutations in the N-RAS and B-RAF genes, in our case, JNK activation was most probably induced as a consequence of minority MOMP (Ichim et al, 2015).…”
Section: Discussionmentioning
confidence: 99%
“…Aside from melanoma, AP-1/ TEADs modulates the expression of a core set of genes involved in migration and invasion of different types of cancer cells, including neuroblastoma, colorectal cancer, and lung cancer (Liu et al, 2016). Regarding the AP-1 transcriptional targets, it is worth noting that melanoma cells failing to die upregulate Cell Reports 31, 107731, June 9, 2020 11 Article ll OPEN ACCESS several genes, such as PTX3, MYLK, SPP1, and RAC2, all shown to be regulated by AP-1 and involved in metastasis (Zhang et al, 2015;Khapchaev and Shirinsky, 2016;Zhuang et al, 2018;Hartl et al, 2006). Although, in these studies, the AP-1/c-JUN transcription factors are activated by a plethora of stimuli, such as cytokines, growth factors, UV irradiation, or activating mutations in the N-RAS and B-RAF genes, in our case, JNK activation was most probably induced as a consequence of minority MOMP (Ichim et al, 2015).…”
Section: Discussionmentioning
confidence: 99%
“…Aside from melanoma, AP-1/TEAD modulates the expression of a core set of genes involved in the migration and invasion of different types of cancer cells, including neuroblastoma, colorectal or lung cancer 42 . Regarding the AP-1 transcriptional targets it is worth noting that melanoma cells failing to die up-regulate several genes such as PTX3 , MYLK , SPP1 or RAC2 , all shown to be regulated by AP-1 and involved in metastasis 43 44 45 46 . While in these studies the AP-1/c-JUN transcription factors are activated by a plethora of stimuli such as cytokines, growth factors, UV irradiation or activating mutations in N-RAS and B-RAF genes, in our case, JNK activation was most probably induced as a consequence of minority MOMP 7 .…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, Jun, Fra-1 [247], and Fos [248] have been shown to be induced in the presence of inactivated GSK3β or increased β-catenin levels. In diseases characterized by augmented amounts of Ser9-phosphorylated GSK3β levels, such as cholestatic liver disease, Jun levels are also increased [249]. However, in some cases, opposed effects have been observed.…”
Section: Ap-1-associated Signalingmentioning
confidence: 99%