Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic liver fibrosis in guinea pigs: A mechanistic approach

Abhilash, Pulanchiyodan; Harikrishnan, Ramasamy; Indira, M.

doi:10.1016/j.taap.2013.11.005

Cited by 31 publications

(25 citation statements)

References 46 publications

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“…Consequentially, NF-jB is translocated to the nucleus and activates NF-jB-mediated transcription of genes, such as cytokines and chemokines (e.g., TGF-b1) . The NF-jB signaling pathway is known as the master regulator of gene expression involved in a wide range of inflammation processes, including liver fibrosis (Tak and Firestein, 2001;Ghosh and Hayden, 2008;Abhilash et al, 2014). NF-jB plays a pivotal role during hepatic fibrogenesis by affecting several biological processes of HSCs.…”

Section: Discussionmentioning

confidence: 99%

“…1A). IjBa also plays an important role in hepatic fibrosis through the NFjB profibrogenic signaling pathway (Abhilash et al, 2014). To delineate potential downstream targets, and further understand the mechanisms of miR-126 upregulation in the pathogenesis of hepatic fibrosis, we selected IjBa for further molecular and functional analysis.…”

Section: Selection Of Potential Downstream Targets Of Mir-126mentioning

confidence: 99%

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Upregulation ofmicroRNA-126in Hepatic Stellate Cells May Affect Pathogenesis of Liver Fibrosis Through theNF-κBPathway

Xiao

Tan

Cheng

et al. 2015

DNA and Cell Biology

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Hepatic fibrosis, which results from chronic liver disease, currently lacks effective treatment. MicroRNAs, a group of small noncoding RNA molecules, have been observed to play an essential role in liver diseases, including hepatic fibrosis. In this study, we described the regulation of nuclear factor kappa B (NF-κB) inhibitor alpha (IκBα) and its possible signaling pathway by miR-126 in human hepatic stellate cell (HSC) line LX-2. The 3'-untranslated region (3'-UTR) of IκBα combined with miR-126 was analyzed by using a dual-luciferase reporter assay. Furthermore, the effects of miR-126 on IκBα mRNA and protein and NF-κB protein expression were assessed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blot analysis in the human HSC LX-2 cell line transfected with miR-126 mimic or inhibitor. Moreover, to understand the molecular mechanism of miR-126 in promoting liver fibrosis through NF-κB signaling pathway, the NF-κB downstream signaling factors expression such as transforming growth factor (TGF)-β1 and collagen I mRNA were detected by real-time qRT-PCR. We identified that IκBα is a potential target gene of miR-126, by directly targeting its 3'-UTR. Endogenous miR-126 and exogenous miR-126 mimic inhibited IκBα expression. Moreover, overexpression of miR-126 reduced total and the cytoplasm IκBα protein expression and increased total and cytoblast NF-κB protein expression of LX-2. Conversely, knockdown of miR-126 could inhibit NF-κB activation by upregulation of IκBα protein expression. Further, miR-126 promoted TNF-a-induced TGF-β1 and collagen I mRNA expression in LX-2 cells. miR-126 may play an important role in hepatic fibrosis by downregulating the expression of IκBα partly through the NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Selection Of Potential Downstream Targets Of Mir-126mentioning

confidence: 99%

Upregulation ofmicroRNA-126in Hepatic Stellate Cells May Affect Pathogenesis of Liver Fibrosis Through theNF-κBPathway

Xiao

Tan

Cheng

et al. 2015

DNA and Cell Biology

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“…Theoretically, the specific regulation of these response transcription factors can cause various changes in pathologies and physiologies. Previous studies have identified the crosstalk between AA and MMP-3 in non-Hodgkin's lymphoma (43), the AA-mediated inhibition of NF-κB leading to the suppression of liver fibrosis (44), the regulatory role of AA in the PKC/Nrf2 pathway (45) and a moderate AA-mediated attenuation of the elevated levels of the AP1 gene induced by H 2 O 2 in the retinal pigment epithelium (31). These findings demonstrate that AA may affect multiple signaling pathways and that the regulatory mechanism in which AA is involved is highly dependent on the microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Ascorbic acid provides protection for human chondrocytes against oxidative stress

Chang

Huo

et al. 2015

Molecular Medicine Reports

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Abstract. Oxidative stress is considered to be an important cause of dysfunction in chondrocytes and articular cartilage degradation, which leads to the pathogenesis of osteoarthritis (OA) and cartilage aging. The present study aimed to assess the effects of the widely applied antioxidant, ascorbic acid (AA), on human chondrocytes against hydrogen peroxide (H 2 O 2 ) in vitro. Using annexin V-fluorescein isothiocyanate, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and senescence-associated β-galactosidase assays, the present study identified that AA reduced apoptosis, reduced the loss of viability and markedly decreased H 2 O 2 -mediated senescence in cells treated with H 2 O 2 . Furthermore, AA not only stimulated the expression levels of collagens and proteoglycans, but also inhibited the differentiation of chondrocytes under conditions of oxidative stress. In addition, reverse transcription-quantitative polymerase chain reaction and western blotting demonstrated that AA decreased the activity of nrf2, NF-κB, AP1 and matrix metalloproteinase-3, which is stimulated by H 2 O 2 . In conclusion, AA efficiently protected human chondrocytes against damage induced by H 2 O 2 by regulating multiple regulatory pathways.

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“…This study also revealed that endocan stimulates nuclear factor kappa β expression (11). Studies have shown that tumour necrosis factor-α and nuclear factor kappa β stimulate liver inflammation and promote liver fibrosis by activating hepatic stellate cells (12,13). Collectively, these effects of endocan on liver inflammation and fibrosis may cause the development of hepatic decompensation in patients with liver cirrhosis.…”

Section: Discussionmentioning

confidence: 54%

Serum Endocan as a Survival Predictor for Patients with Liver Cirrhosis

Toshikuni

Ozaki

George

et al. 2015

Canadian Journal of Gastroenterology and Hepatology

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BACKGROUND: The relationship between endocan expression and outcome in patients with chronic liver disease is not fully understood.OBJECTIVE: To examine whether serum endocan level is predictive of outcome in patients with liver cirrhosis.METHODS: A total of 68 patients with liver cirrhosis were enrolled. Outcome predictors were analyzed using the Cox proportional hazards model. The overall survival rates were calculated using the Kaplan-Meier method, and differences were evaluated using the log-rank test.RESULTS: During the median follow-up period (7.1 years), nine patients had hepatocellular carcinoma (HCC) and 10 patients died. Of the deceased patients, nine died due to hepatic decompensation or associated conditions. No significant factors were found to be predictive of the occurrence of HCC. In contrast, an elevated serum endocan level (≥2.0 ng/mL; HR 2.34 [95% CI 1.05 to 7.03]; P=0.037) and high Child-Pugh grade B/C (HR 2.65 [95% CI 1.30 to 6.89; P=0.006) were predictive of poor survival. Kaplan-Meier analysis revealed that the respective cumulative survival rates at five and 10 years were 97.1% and 87.4% in patients with serum endocan levels <2.0 ng/mL and 85.8% and 64.4% in patients with levels ≥2.0 ng/mL (P=0.009), respectively. Moreover, the cumulative survival rates were significantly different among the patient groups divided according to serum endocan level and Child-Pugh grade (P=0.002).CONCLUSION: These findings suggest that serum endocan level may be a survival predictor for patients with liver cirrhosis.

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Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic liver fibrosis in guinea pigs: A mechanistic approach

Cited by 31 publications

References 46 publications

Upregulation ofmicroRNA-126in Hepatic Stellate Cells May Affect Pathogenesis of Liver Fibrosis Through theNF-κBPathway

Upregulation ofmicroRNA-126in Hepatic Stellate Cells May Affect Pathogenesis of Liver Fibrosis Through theNF-κBPathway

Ascorbic acid provides protection for human chondrocytes against oxidative stress

Serum Endocan as a Survival Predictor for Patients with Liver Cirrhosis

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