Redox cell signaling and hepatic progenitor cells

Bello, Giorgia di; Vendemiale, Gianluigi; Bellanti, Francesco

doi:10.1016/j.ejcb.2018.09.004

Cited by 14 publications

(7 citation statements)

References 175 publications

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“…Reactive species modulate and are modulated by several factors including the nuclear factor (erythroid-derived 2)-like 2 (NRF2), Forkhead box O (FoxO) family, glycogen synthase kinase (GSK-3β), the PR domain containing 16 (PRDM16), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), the p53 (TRP53) tumor suppressor, Wnt and nucleoredoxin (Nrx) 10 – 16 . These transcription factors may be involved in the regulation of quiescence/self-renewal/differentiation of several stem cell lines 17 . However, to date a direct regulation of HPCs by redox signaling has not been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of nuclear factor (erythroid-derived 2)-like 2 promotes hepatic progenitor cell activation and differentiation

et al. 2021

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The stem cell ability to self-renew and lead regeneration relies on the balance of complex signals in their microenvironment. The identification of modulators of hepatic progenitor cell (HPC) activation is determinant for liver regeneration and may improve cell transplantation for end-stage liver disease. This investigation used different models to point out the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) as a key regulator of the HPC fate. We initially proved that in vivo models of biliary epithelial cells (BECs)/HPC activation show hepatic oxidative stress, which activates primary BECs/HPCs in vitro. NRF2 downregulation and silencing were associated with morphological, phenotypic, and functional modifications distinctive of differentiated cells. Furthermore, NRF2 activation in the biliary tract repressed the ductular reaction in injured liver. To definitely assess the importance of NRF2 in HPC biology, we applied a xenograft model by inhibiting NRF2 in the human derived HepaRG cell line and transplanting into SCID/beige mice administered with anti-Fas antibody to induce hepatocellular apoptosis; this resulted in effective human hepatocyte repopulation with reduced liver injury. To conclude, NRF2 inhibition leads to the activation and differentiation of liver progenitors. This redox-dependent transcription factor represents a potential target to regulate the commitment of undifferentiated hepatic progenitors into specific lineages.

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Section: Introductionmentioning

confidence: 99%

Inhibition of nuclear factor (erythroid-derived 2)-like 2 promotes hepatic progenitor cell activation and differentiation

et al. 2021

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“…Concurrently, the association between high levels of oxidative stress and a reduction of antioxidant defenses has also been reported in most of these pathological situations [8, 9]. According to the results obtained by several studies, the imbalance between the production of ROS and antioxidant defense in some of these liver diseases affects liver regeneration [10–12]. One of the reasons that explain this ROS effect is that ROS modulates the expression of a variety of regulators that play major roles in liver regeneration, including growth factors, transcription factors and cell cycle proteins such as β-catenin [13], cyclin D [14], p53 [15], Nrf2 [16] and JNK/p38 mitogen activated kinases [17].…”

Section: Introductionmentioning

confidence: 99%

Cerium oxide nanoparticles improve liver regeneration after acetaminophen-induced liver injury and partial hepatectomy in rats

et al. 2019

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Background and aimsCerium oxide nanoparticles are effective scavengers of reactive oxygen species and have been proposed as a treatment for oxidative stress-related diseases. Consequently, we aimed to investigate the effect of these nanoparticles on hepatic regeneration after liver injury by partial hepatectomy and acetaminophen overdose.MethodsAll the in vitro experiments were performed in HepG2 cells. For the acetaminophen and partial hepatectomy experimental models, male Wistar rats were divided into three groups: (1) nanoparticles group, which received 0.1 mg/kg cerium nanoparticles i.v. twice a week for 2 weeks before 1 g/kg acetaminophen treatment, (2) N-acetyl-cysteine group, which received 300 mg/kg of N-acetyl-cysteine i.p. 1 h after APAP treatment and (3) partial hepatectomy group, which received the same nanoparticles treatment before partial hepatectomy. Each group was matched with vehicle-controlled rats.ResultsIn the partial hepatectomy model, rats treated with cerium oxide nanoparticles showed a significant increase in liver regeneration, compared with control rats. In the acetaminophen experimental model, nanoparticles and N-acetyl-cysteine treatments decreased early liver damage in hepatic tissue. However, only the effect of cerium oxide nanoparticles was associated with a significant increment in hepatocellular proliferation. This treatment also reduced stress markers and increased cell cycle progression in hepatocytes and the activation of the transcription factor NF-κB in vitro and in vivo.ConclusionsOur results demonstrate that the nanomaterial cerium oxide, besides their known antioxidant capacities, can enhance hepatocellular proliferation in experimental models of liver regeneration and drug-induced hepatotoxicity.

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“…Liver links the digestive tract and general circulation, and plays a central role in nutrient metabolism, synthesis of functional proteins and detoxification of drugs and chemicals [1, 2]. Liver is subjected to various diseases which may be metabolic, toxin/chemical-induced tissue inflammation or viral hepatitis B/C-associated cirrhosis and carcinomas.…”

Section: Introductionmentioning

confidence: 99%

“…Liver is subjected to various diseases which may be metabolic, toxin/chemical-induced tissue inflammation or viral hepatitis B/C-associated cirrhosis and carcinomas. Chronic liver disease is the fifth most common cause of mortality, worldwide where the casualty rate is increasing despite of advances in therapeutics [2]. Therefore, there is an essential need to search for new anti-hepatitis and hepatoprotective agents [3].…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective effect of Solanum surattense leaf extract against chemical- induced oxidative and apoptotic injury in rats

Parvez

Al‐Dosari

Arbab

et al. 2019

BMC Complement Altern Med

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Background Of over 35 Saudi plants traditionally used to treat liver disorders, majority still lack scientific validations. We therefore, evaluated the anti-oxidative, anti-apoptotic and hepatoprotective potential of Solanum surattense leaves total ethanol-extract (SSEE). Methods The cytoprotective (4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide/ MTT assay) and anti-apoptotic (caspase-3/7) potential of SSEE (25–200 μg/mL) were assessed in cultured HepG2 cells against dichlorofluorescein (DCFH)-induced toxicity. The hepatoprotective salutation of SSEE (100 and 200 mg/kg.bw/day) in carbon tetrachloride (CCl 4 )-intoxicated rats was evaluated by serum biochemistry and histopathology. The anti-oxidative activity of SSEE (31.25–500 μg/mL) was tested by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging and linoleic acid bleaching assays. Also, SSEE was subjected to qualitative phytochemical analysis, and standardized by validated high-performance liquid chromatography (HPTLC). Results SSEE at doses 50, 100 and 200 μg/mL showed HepG2 cell proliferative and protective potential by about 61.0, 67.2 and 95%, respectively through inhibition of caspase-3/7 against DCFH-toxicity. In CCl 4 -injured rats, SSEE (200 mg/kg) significantly ( P < 0.001) normalized serum transaminases, alkaline phosphatase, bilirubin, cholesterol, triglycerides, and total protein, including tissue malondialdehyde and nonprotein sulfhydryls levels, supported by the liver histopathology. SSEE further showed strong in vitro anti-oxidative and anti-lipid peroxidative activities, evidenced by the presence of alkaloids, flavonoids, tannins, sterols and saponins. Identification of β-sitosterol (3.46 μg/mg) strongly supported the anti-oxidative and hepatoprotective salutation of SSEE. Conclusion Our findings suggest the therapeutic potential of S. surattense against chemical-induced oxidative stress and liver damage. However, isolation of the active principles and elucidation of mechanism of action remain to be addressed.

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Redox cell signaling and hepatic progenitor cells

Cited by 14 publications

References 175 publications

Inhibition of nuclear factor (erythroid-derived 2)-like 2 promotes hepatic progenitor cell activation and differentiation

Inhibition of nuclear factor (erythroid-derived 2)-like 2 promotes hepatic progenitor cell activation and differentiation

Cerium oxide nanoparticles improve liver regeneration after acetaminophen-induced liver injury and partial hepatectomy in rats

Hepatoprotective effect of Solanum surattense leaf extract against chemical- induced oxidative and apoptotic injury in rats

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