Vitamin D Receptor Activation Targets ROS-Mediated Crosstalk Between Autophagy and Apoptosis in Hepatocytes in Cholestasic Mice

Zhi-Jian, Zheng; Xie, Jing; Ma, Liman; Hao, Zhiqing; Zhang, Weiwei; Li, Lihua

doi:10.1016/j.jcmgh.2022.10.011

Cited by 14 publications

(5 citation statements)

References 61 publications

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“…To better confirm the potential signaling pathway after ritanserin treatment, we performed rescue experiments through the potent MAPK, MEK/ERK agonists C16-PAF [ 27 ], and the JAK/STAT agonists RO8191 [ 28 ]. Compared with the ritanserin monotherapy, C16-PAF or RO8191 combined with ritanserin were revealed to increase cell proliferation and inhibit apoptosis in AML cells, accompanied by statistical differences (Fig.…”

Section: Resultsmentioning

confidence: 99%

Ritanserin suppresses acute myeloid leukemia by inhibiting DGKα to downregulate phospholipase D and the Jak-Stat/MAPK pathway

Tan

Zhong

et al. 2023

Discov Onc

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Refractory or relapsed (R/R) AML is the most challenging form of AML to treat. Due to frequent genetic mutations, therapy alternatives are limited. Here, we identified the role of ritanserin and its target DGKα in AML. Several AML cell lines and primary patient cells were treated with ritanserin and subjected to cell proliferation, apoptosis and gene analyses with CCK-8 assay, Annexin V/PI assay and Western blotting, respectively. We also evaluated the function of the ritanserin target diacylglycerol kinase alpha (DGKα) in AML by bioinformatics. In vitro experiments have revealed that ritanserin inhibits AML progression in a dose- and time-dependent manner, and it shows an anti-AML effect in xenograft mouse models. We further demonstrated that the expression of DGKα was elevated in AML and correlated with poor survival. Mechanistically, ritanserin negatively regulates SphK1 expression through PLD signaling, also inhibiting the Jak-Stat and MAPK signaling pathways via DGKα. These findings suggest that DGKα may be an available therapeutic target and provide effective preclinical evidence of ritanserin as a promising treatment for AML.

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Section: Resultsmentioning

confidence: 99%

Ritanserin suppresses acute myeloid leukemia by inhibiting DGKα to downregulate phospholipase D and the Jak-Stat/MAPK pathway

Tan

Zhong

et al. 2023

Discov Onc

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“…Previous studies showed that the VDR–YAP axis promotes cholangiocyte proliferation and enhances adaptive bile duct remodeling, alleviating cholestatic liver injury in BDL mice [ 126 ]. VDR activation mitigated cholestatic liver injury by reducing autophagy-dependent hepatocyte apoptosis and suppressing the activation of the ROS-dependent ERK/p38MAPK pathway [ 127 ]. While modulating VDR activity may be a potential target for treating cholestatic liver diseases, it is important to note that VDR activity can affect calcium metabolism and influence blood calcium levels.…”

Section: Bas In Cholestatic Liver Diseasesmentioning

confidence: 99%

Bile acid-mediated signaling in cholestatic liver diseases

Zeng¹,

Fan²,

Zhou³

2023

Cell Biosci

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Chronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are associated with bile stasis and gradually progress to fibrosis, cirrhosis, and liver failure, which requires liver transplantation. Although ursodeoxycholic acid is effective in slowing the disease progression of PBC, it has limited efficacy in PSC patients. It is challenging to develop effective therapeutic agents due to the limited understanding of disease pathogenesis. During the last decade, numerous studies have demonstrated that disruption of bile acid (BA) metabolism and intrahepatic circulation promotes the progression of cholestatic liver diseases. BAs not only play an essential role in nutrition absorption as detergents but also play an important role in regulating hepatic metabolism and modulating immune responses as key signaling molecules. Several excellent papers have recently reviewed the role of BAs in metabolic liver diseases. This review focuses on BA-mediated signaling in cholestatic liver disease.

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“…Moreover, HCC can be classified by major molecular drivers and pathways, which are associated with specific genomic disorders, histopathological fingerprints, and clinical outcomes 5,6 . The main signaling pathways that have been demonstrated include PI3K/Akt/mTOR signaling, Wnt/TGF‐β signaling, Ras/MAPK signaling, and MET and IGF signaling 7–9 …”

Section: Introductionmentioning

confidence: 99%

“…5,6 The main signaling pathways that have been demonstrated include PI3K/Akt/mTOR signaling, Wnt/TGF-β signaling, Ras/MAPK signaling, and MET and IGF signaling. [7][8][9] The PI3K signaling pathway is vital for growth, differentiation, and survival. Recent research has uncovered isoform-specific regulation in class IA and IB PI3Ks 10 with regulatory subunits playing a crucial role.…”

Section: Introductionmentioning

confidence: 99%

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PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A

Lin

Wang

et al. 2023

Cancer Medicine

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Vitamin D Receptor Activation Targets ROS-Mediated Crosstalk Between Autophagy and Apoptosis in Hepatocytes in Cholestasic Mice

Cited by 14 publications

References 61 publications

Ritanserin suppresses acute myeloid leukemia by inhibiting DGKα to downregulate phospholipase D and the Jak-Stat/MAPK pathway

Ritanserin suppresses acute myeloid leukemia by inhibiting DGKα to downregulate phospholipase D and the Jak-Stat/MAPK pathway

Bile acid-mediated signaling in cholestatic liver diseases

PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A

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