mRNA sequencing and CyTOF analysis revealed ASPP2 altered the response patterns of hepatocellular carcinoma HepG2 cells to usnic acid

Wang, Yan; Yan, Yadong; Huo, Yunfei; Pang, Yuheng; Chan, Liujia; Wang, Shanshan; Chen, Dexi; Lin, Dongdong; Wang, Wenjing

doi:10.1007/s00210-023-02428-2

Cited by 2 publications

(3 citation statements)

References 24 publications

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“…Time‑of‑flight mass cytometry was performed for analysis of the expression of the 26 related proteins in atRA-treated HepaRG cells as described 33 . Briefly, HepaRG cells were harvested and labeled with cisplatin to distinguish the dead cells.…”

Section: Methodsmentioning

confidence: 99%

“…Time‑of‑flight mass cytometry was performed for analysis of the expression of the 26 related proteins in atRA-treated HepaRG cells as described. 33 Briefly, HepaRG cells were harvested and labeled with cisplatin to distinguish the dead cells. Then, the cells were stained with an antibody cocktail against target markers and DNA intercalator.…”

Section: Methodsmentioning

confidence: 99%

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Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure

Wang,

Link,

Munker

et al. 2024

Hepatology Communications

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Background: When massive necrosis occurs in acute liver failure (ALF), rapid expansion of HSCs called liver progenitor cells (LPCs) in a process called ductular reaction is required for survival. The underlying mechanisms governing this process are not entirely known to date. In ALF, high levels of retinoic acid (RA), a molecule known for its pleiotropic roles in embryonic development, are secreted by activated HSCs. We hypothesized that RA plays a key role in ductular reaction during ALF. Methods: RNAseq was performed to identify molecular signaling pathways affected by all-trans retinoid acid (atRA) treatment in HepaRG LPCs. Functional assays were performed in HepaRG cells treated with atRA or cocultured with LX-2 cells and in the liver tissue of patients suffering from ALF. Results: Under ALF conditions, activated HSCs secreted RA, inducing RARα nuclear translocation in LPCs. RNAseq data and investigations in HepaRG cells revealed that atRA treatment activated the WNT-β-Catenin pathway, enhanced stemness genes (SOX9, AFP, and others), increased energy storage, and elevated the expression of ATP-binding cassette transporters in a RARα nuclear translocation-dependent manner. Further, atRA treatment–induced pathways were confirmed in a coculture system of HepaRG with LX-2 cells. Patients suffering from ALF who displayed RARα nuclear translocation in the LPCs had significantly better MELD scores than those without. Conclusions: During ALF, RA secreted by activated HSCs promotes LPC activation, a prerequisite for subsequent LPC-mediated liver regeneration.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure

Wang,

Link,

Munker

et al. 2024

Hepatology Communications

Self Cite

View full text Add to dashboard Cite

show abstract

“…Time-of-flight mass cytometry was performed for analysis of expression of the 26 related proteins in atRA treated HepaRG cells as previously described (33). Briefly, HepaRG cells were harvested and labelled with Cisplatin to distinguish the dead cells.…”

Section: Time-of-flight Mass Cytometrymentioning

confidence: 99%

Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure

Wang,

Link,

Munker

et al. 2024

Preprint

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Objective: When massive necrosis occurs in acute liver failure (ALF), rapid expansion of hepatic stem cells called liver progenitor cells (LPC) in a process called ductular reaction (DR) is required for survival. The exact underlying mechanisms of this process are not known to date. In ALF, high levels of retinoic acid (RA), a molecule known for its pleiotropic roles in embryonic development, are secreted by activated hepatic stellate cells (HSCs). We hypothesized that RA plays a key role during DR. Methods: RNA-Seq was performed to identify molecular signaling pathways affected by all-trans retinoid acid (atRA) treatment in HepaRG LPC cells in vitro. Functional assays for RA were performed in HepaRG cells with atRA treatment as well as co-culture with LX-2 cells in vitro, and liver tissue of patients suffering from ALF in vivo. Results: Under ALF conditions, activated HSCs secreted RA, inducing RARα nuclear translocation in LPCs. RNA-seq data and investigations in HepaRG cells revealed that atRA treatment activated the WNT-β-Catenin pathway, enhanced stemness genes (SOX9, AFP, et.al), promoted energy storage, and elevated the expression of ATP-binding cassette (ABC) transporters depending on RARα nuclear translocation. Further, atRA treatment-induced pathways were confirmed in a co-culture system of HepaRG with LX-2 cells. Patients with ALF who displayed RARα nuclear translocation in LPC had significantly better MELD scores than those without. Conclusion: In ALF, RA secreted by activated hepatic stellate cells promotes LPC activation, a prerequisite for subsequent LPC-mediated liver regeneration.

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mRNA sequencing and CyTOF analysis revealed ASPP2 altered the response patterns of hepatocellular carcinoma HepG2 cells to usnic acid

Cited by 2 publications

References 24 publications

Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure

Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure

Retinoic acid generates a beneficial microenvironment for liver progenitor cell activation in acute liver failure

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