Augmenter of liver regeneration: Mitochondrial function and steatohepatitis

Verma, Alok; Sharma, Akanksha; Nithyananthan, Subramaniyam; Gandhi, Chandrashekhar R.

doi:10.1016/j.jhep.2022.06.019

Cited by 20 publications

(13 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…26 It has been reported that ALR was as strong or stronger than transforming growth factor alpha (TGF-α) or human growth factor as a mitogen for hepatocytes. 27 In a previous study, we found that blocking extracellular 15-kD-ALR with an anti-ALR antibody decreased U266-cell proliferation in multiple myeloma by via the mitogen-activated protein kinase and cell cycle signaling pathways. 12 However, the role of ALR-specific mAb in HCC is not clear.…”

Section: Discussionmentioning

confidence: 88%

“…26 The short 15 kD form of human recombinant ALR is mainly found in the cytoplasm and nucleus. 27 Most important, it is secreted into extracellular environments, where it has important roles in liver regeneration, promotion of polyamine synthesis, and maintaining other physiological functions in cells. 26 It has been reported that ALR was as strong or stronger than transforming growth factor alpha (TGF-α) or human growth factor as a mitogen for hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Augmenter of Liver Regeneration Monoclonal Antibody Promotes Apoptosis of Hepatocellular Carcinoma Cells

Huang¹,

Luo²,

Huang³

et al. 2023

J Clin Transl Hepatol

View full text Add to dashboard Cite

Background and Aims: Hepatocellular carcinoma (HCC) is one of the most common types of cancer, often resulting in death. Augmenter of liver regeneration (ALR), a widely expressed multifunctional protein, has roles in liver disease. In our previous study, we reported that ALR knockdown inhibited cell proliferation and promoted cell death. However, there is no study on the roles of ALR in HCC. Methods: We used in vitro and in vivo models to investigate the effects of ALR in HCC as well as its mechanism of action. We produced and characterized a human ALRspecific monoclonal antibody (mAb) and investigated the effects of the mAb in HCC cells. Results: The purified ALRspecific mAb matched the predicted molecular weight of IgG heavy and light chains. Thereafter, we used the ALRspecific mAb as a therapeutic strategy to suppress tumor growth in nude mice. Additionally, we assessed the proliferation and viability of three HCC cell lines, Hep G2, Huh-7, and MHC97-H, treated with the ALR-specific mAb. Compared with controls, tumor growth was inhibited in mice treated with the ALR-specific mAb at 5 mg/kg, as shown by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling. Simultaneous treatment with the ALR-specific mAb and adriamycin promoted apoptosis, whereas treatment with the ALR-specific mAb alone inhibited cell proliferation. Conclusions: The ALR-specific mAb might be a novel therapy for HCC by blocking extracellular ALR.

show abstract

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Augmenter of Liver Regeneration Monoclonal Antibody Promotes Apoptosis of Hepatocellular Carcinoma Cells

Huang¹,

Luo²,

Huang³

et al. 2023

J Clin Transl Hepatol

View full text Add to dashboard Cite

show abstract

“…In recent years, oxidative stress has been considered as a conjoint pathological mechanism in drug-induced liver injury and other liver diseases. − Excessive ROS attacks numerous biomolecules, such as DNA, proteins, and lipids. As a key regulator of oxidative stress and ROS generation, NRF2 is a novel therapeutic target for liver disease treatment. ,,, The expression of diverse antioxidant enzymes is directly regulated by NRF2, which holds important position in the deletion of free radicals .…”

Section: Discussionmentioning

confidence: 99%

Liquiritigenin Confers Liver Protection by Enhancing NRF2 Signaling through Both Canonical and Non-canonical Signaling Pathways

Shi

Zhang

et al. 2023

J. Med. Chem.

View full text Add to dashboard Cite

Oxidative stress plays a critical role in drug-induced liver injury. In recent years, liquiritigenin (LQ), a natural flavonoid distributed in Glycyrrhizae Radix et Rhizoma (Gan Cao), shows protective effects against oxidative hepatotoxicity. However, the underlying mechanism remains unclear. In this study, we mainly investigated the role of NRF2, a core transcription factor in oxidative stress, in LQ-induced hepatoprotection. Our results indicated that the function of LQ to eliminate reactive oxygen species in liver cells was dependent on NRF2 activation. Both a canonical signaling pathway and a non-canonical signaling pathway are involved in LQ-induced NRF2 activation. LQ induced NRF2 activation in a KEAP1-C151-dependent manner partially. Meanwhile, LQ led to the blockage of autophagic flux and upregulation of p62, which competitively bound with KEAP1 and conferred NRF2 activation in a KEAP1-C151-independent manner. Totally, our study reveals a novel molecular mechanism underlying the hepatoprotection of LQ, providing a new insight into the pathogenesis and therapeutic strategy of oxidative liver injury.

show abstract

“…Studies of senescent cells also indicated that nicotinamide adenine dinucleotide (NAD), silence information regulator protein family (sirtuins), and mechanistic target of rapamycin (mTOR) were the major signaling pathways involved in NASH-driven HCC [ 33 ]. Augmenter of liver regeneration (ALR) is an important enzyme to maintain mitochondrial dynamics [ 34 ]. Zheng et al proved that the ubiquitination degradation of ALR had a potential contribution to NASH-driven HCC progression at the mitochondrial level [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

A Multi-Omics Analysis of NASH-Related Prognostic Biomarkers Associated with Drug Sensitivity and Immune Infiltration in Hepatocellular Carcinoma

Liu

Jiang

Zhou

et al. 2023

JCM

View full text Add to dashboard Cite

Background: Nonalcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is becoming a major health-related problem. The exploration of NASH-related prognostic biomarkers and therapeutic targets is necessary. Methods: Data were downloaded from the GEO database. The “glmnet” package was used to identify differentially expressed genes (DEGs). The prognostic model was constructed by the univariate Cox and LASSO regression analyses. Validation of the expression and prognosis by immunohistochemistry (IHC) in vitro. Drug sensitivity and immune cell infiltration were analyzed by CTR-DB and ImmuCellAI. Results: We constructed a prognostic model that identified the NASH-related gene set (DLAT, IDH3B, and MAP3K4), which was validated in a real-world cohort. Next, seven prognostic transcription factors (TFs) were identified. The prognostic ceRNA network included three mRNAs, four miRNAs, and seven lncRNAs. Finally, we found that the gene set was associated with drug response which was validated in six clinical trial cohorts. Moreover, the expression level of the gene set was inversely correlated with CD8 T cell infiltration in HCC. Conclusions: We established a NASH-related prognostic model. Upstream transcriptome analysis and the ceRNA network provided clues for mechanism exploration. The mutant profile, drug sensitivity, and immune infiltration analysis further guided precise diagnosis and treatment strategies.

show abstract

Augmenter of liver regeneration: Mitochondrial function and steatohepatitis

Cited by 20 publications

References 108 publications

Augmenter of Liver Regeneration Monoclonal Antibody Promotes Apoptosis of Hepatocellular Carcinoma Cells

Augmenter of Liver Regeneration Monoclonal Antibody Promotes Apoptosis of Hepatocellular Carcinoma Cells

Liquiritigenin Confers Liver Protection by Enhancing NRF2 Signaling through Both Canonical and Non-canonical Signaling Pathways

A Multi-Omics Analysis of NASH-Related Prognostic Biomarkers Associated with Drug Sensitivity and Immune Infiltration in Hepatocellular Carcinoma

Contact Info

Product

Resources

About