scholarly journals TMEM88 Modulates Lipid Synthesis and Metabolism Cytokine by Regulating Wnt/β-Catenin Signaling Pathway in Non-Alcoholic Fatty Liver Disease

2022 ◽  
Vol 12 ◽  
Author(s):  
Huan Zhou ◽  
Xingyu Zhu ◽  
Yan Yao ◽  
Yue Su ◽  
Jing Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Western Blotting ◽  
Lipid Synthesis ◽  
Alcoholic Fatty Liver ◽  
Downstream Target ◽  
New Ideas ◽  
Mice Liver ◽  
Alcoholic Fatty Liver Disease

Objective: To clarify the molecular mechanism of TMEM88 regulating lipid synthesis and metabolism cytokine in NAFLD.Methods:In vivo, NAFLD model mice were fed by a Methionine and Choline-Deficient (MCD) diet. H&E staining and immunohistochemistry experiments were used to analyze the mice liver tissue. RT-qPCR and Western blotting were used to detect the lipid synthesis and metabolism cytokine. In vitro, pEGFP-C1-TMEM88 and TMEM88 siRNA were transfected respectively in free fat acid (FFA) induced AML-12 cells, and the expression level of SREBP-1c, PPAR-α, FASN, and ACOX-1 were evaluated by RT-qPCR and Western blotting.Results: The study found that the secretion of PPAR-α and its downstream target ACOX-1 were upregulated, and the secretion of SREBP-1c and its downstream target FASN were downregulated after transfecting with pEGFP-C1-TMEM88. But when TMEM88 was inhibited, the experimental results were opposite to the aforementioned conclusions. The data suggested that it may be related to the occurrence, development, and end of NAFLD. Additionally, the study proved that TMEM88 can inhibit Wnt/β-catenin signaling pathway. Meanwhile, TMEM88 can accelerate the apoptotic rate of FFA-induced AML-12 cells.Conclusion: Overall, the study proved that TMEM88 takes part in regulating the secretion of lipid synthesis and metabolism cytokine through the Wnt/β-catenin signaling pathway in AML-12 cells. Therefore, TMEM88 may be involved in the progress of NAFLD. Further research will bring new ideas for the study of NAFLD.

scholarly journals JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level

2020 ◽  
Author(s):  
Da Huang ◽  
Fan Xiao ◽  
Fuzhou Hua ◽  
Zhenzhong Luo ◽  
Zhaoxia Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Critical Role ◽  
Predictive Marker ◽  
Cancer Proliferation ◽  
Poor Overall Survival ◽  
Downstream Target ◽  
Cellular Analysis

Abstract Background: Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Nevertheless, its functional role in colorectal cancer (CRC) progression is not fully understood. Methods: Herein, JARID1B expression levels were detected in clinical CRC samples by western blotting and qRT-PCR. DLD-1 cells with JARID1B knockdown or overexpression by stably transfected plasmids were used in vitro and in vivo study. Colony formation, 5-ethynyl-20-deoxyuridine (EdU) and Real Time Cellular Analysis(RTCA) assays were used to detect cell proliferation and growth. Transcriptome and CHIP assays were used to examine the molecular biology changes and molecular interaction in these cells. Nude mice was utilized to study the correlation of JARID1B and tumor growth in vivo. Results: Here, we first observed that JARID1B was significantly upregulated in CRC tissue compared to adjacent normal tissues. In CRC patients, JARID1B high expression was positively relation with poor overall survival. Multivariate analyses revealed that high JARID1B expression was an independent predictive marker for the poor prognosis of CRC. In addition, we found that JARID1B promoted CRC cells proliferation by Wnt/β-catenin signaling pathway. Further studies demonstrated CDX2 as a downstream target of JARID1B, and our data demonstrated that CDX2 is crucial for JARID1B -mediated Wnt/β-catenin signaling pathway. Mechanistically, we demonstrated that JARID1B regulated CDX2 expression through demethylation of H3K4me3. Conclusions: CDX2 inhibited by JARID1B-derived H3K4me3 methylation promoted cells proliferation of CRC via Wnt/β-catenin signaling pathway. Therefore, our studies provided a novel insight into the role of JARID1B in CRC cells proliferation and potential new molecular target for treating CRC.

scholarly journals Naringin protects against non-alcoholic fatty liver disease by promoting autophagic flux and lipophagy

2021 ◽  
Author(s):  
Lingling Guan ◽  
Lan Guo ◽  
Heng Zhang ◽  
Hao Liu ◽  
Yuan Qiao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Autophagic Flux ◽  
Mechanism Study ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background and Purpose: The autophagic degradation of lipid droplets (LDs), termed lipophagy, is the main mechanism contributing to lipid consumption in hepatocytes. The identification of effective and safe natural compounds that target lipophagy to eliminate excess lipids may be a potential therapeutic strategy for non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effects of naringin on NAFLD and the underlying mechanism. Experimental Approach: The role of naringin was investigated in mice fed a high-fat diet (HFD) to induce NAFLD, as well as in AML12 cells and primary hepatocytes stimulated by palmitate (PA). Transcription factor EB (TFEB)-knockdown AML12 cells and hepatocyte-specific TFEB-knockout mice were also used for the mechanism study. In vivo and in vitro studies were conducted using transmission electron microscopy, immunofluorescence techniques and western blot analysis. Key Results: We found that naringin treatment effectively relieved HFD-induced hepatic steatosis in mice and inhibited palmitate (PA)-induced lipid accumulation in hepatocytes. The increased p62 and LC3-II levels observed with excess lipid-support autophagosome accumulation and impaired autophagic flux. Treatment with naringin restored TFEB-mediated lysosomal biogenesis, thereby promoting the fusion of autophagosomes and lysosomes, restoring impaired autophagic flux and further inducing lipophagy. However, the knockdown of TFEB in hepatocytes or the hepatocyte-specific knockout of TFEB in mice abrogated naringin-induced lipophagy, which eliminated the therapeutic effect of naringin on hepatic steatosis. Conclusion and Implications: These results demonstrate that TFEB-mediated lysosomal biogenesis and subsequent lipophagy play essential roles in the ability of naringin to mitigate hepatic steatosis and suggest that naringin is a promising drug for treating or relieving NAFLD.

scholarly journals JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level

2020 ◽  
Author(s):  
Da Huang ◽  
Fan Xiao ◽  
Haibin Hao ◽  
Fuzhou Hua ◽  
Zhenzhong Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Critical Role ◽  
Predictive Marker ◽  
Cancer Proliferation ◽  
Poor Overall Survival ◽  
Downstream Target ◽  
Cellular Analysis

Abstract Background: Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Nevertheless, its functional role in colorectal cancer (CRC) progression is not fully understood.Methods: Herein, JARID1B expression levels were detected in clinical CRC samples by western blotting and qRT-PCR. DLD-1 cells with JARID1B knockdown or overexpression by stably transfected plasmids were used in vitro and in vivo study. Colony formation, 5-ethynyl-20-deoxyuridine (EdU) and Real Time Cellular Analysis(RTCA) assays were used to detect cell proliferation and growth. Transcriptome and CHIP assays were used to examine the molecular biology changes and molecular interaction in these cells. Nude mice was utilized to study the correlation of JARID1B and tumor growth in vivo.Results: Here, we first observed that JARID1B was significantly upregulated in CRC tissue compared to adjacent normal tissues. In CRC patients, JARID1B high expression was positively relation with poor overall survival. Multivariate analyses revealed that high JARID1B expression was an independent predictive marker for the poor prognosis of CRC. In addition, we found that JARID1B promoted CRC cells proliferation by Wnt/β-catenin signaling pathway. Further studies demonstrated CDX2 as a downstream target of JARID1B, and our data demonstrated that CDX2 is crucial for JARID1B -mediated Wnt/β-catenin signaling pathway. Mechanistically, we demonstrated that JARID1B regulated CDX2 expression through demethylation of H3K4me3.Conclusions: CDX2 inhibited by JARID1B-derived H3K4me3 methylation promoted cells proliferation of CRC via Wnt/β-catenin signaling pathway. Therefore, our studies provided a novel insight into the role of JARID1B in CRC cells proliferation and potential new molecular target for treating CRC.

scholarly journals Fuzi-lizhong Decoction Alleviate Nonalcoholic Fatty Liver Disease by Blocking TLR4/MyD88/TRAF6 Signaling Pathway

2021 ◽  
Author(s):  
Ying Zhang ◽  
Jiayao Yang ◽  
Wei Ma ◽  
Hongfeng Yi ◽  
Yan Liao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Blood Glucose ◽  
Fatty Liver ◽  
Total Cholesterol ◽  
Signaling Pathway ◽  
Fatty Liver Disease ◽  
Quantitative Polymerase Chain Reaction ◽  
Alcoholic Fatty Liver

Abstract Background Fuzi-lizhong decoction (FLD) derives from an ancient Chinese Pharmacopoeia and has been used for the clinical treatment for years. The present study aimed to investigate the activities and underlying mechanisms of FLD against non-alcoholic fatty liver disease (NAFLD). Methods In vivo NAFLD in rats was induced by high-fat diet, and in vitro studies were performed on HL-7702 cells treated with oleic and linoleic. Serum levels of total cholesterol (TC), triglyceride (TG) and blood glucose (Glu) were detected using an automatic biochemical analyzer. Expression of IL-2, IL-6 and TNFα were detected by ELISA. Using the Western blot (WB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to measure the levels of TLR4, MyD88 and TRAF6.Results FLD significantly attenuated inflammation and improved collagen accumulation through down-regulating the levels of IL-2, IL-6, TNFα, NF-κB p65 by inhibited the activation of TLR4/MyD88/TRAF6 signaling pathway both in vivo and in vitro. TLR 4 overexpression in NAFLD was decreased by FLD, leading to the markedly down-regulated levels of myeloid differentiation factor 88 (MyD88) and TNF receptor associated factor 6 (TRAF6). In addition, the significant increased levels of total cholesterol (TC), triglyceride (TG) and blood glucose (Glu) in serum and free fatty acid (FFA) in liver were significant reduced by FLD treatment. Conclusions FLD exhibited potent protective effect against NAFLD via TLR4/MyD88/TRAF6 signaling pathway, which might provide a novel insight into the mechanisms of this compound as an anti-inflammatory candidate for the treatment of ALF in the future.

scholarly journals JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level

2020 ◽  
Author(s):  
Da Huang ◽  
Fan Xiao ◽  
Haibin Hao ◽  
Fuzhou Hua ◽  
Zhenzhong Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Critical Role ◽  
Predictive Marker ◽  
Cancer Proliferation ◽  
Poor Overall Survival ◽  
Downstream Target ◽  
Cellular Analysis

Abstract Background: Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Nevertheless, its functional role in colorectal cancer (CRC) progression is not fully understood.Methods: Herein, JARID1B expression levels were detected in clinical CRC samples by western blotting and qRT-PCR. DLD-1 cells with JARID1B knockdown or overexpression by stably transfected plasmids were used in vitro and in vivo study. Colony formation, 5-ethynyl-20-deoxyuridine (EdU) and Real Time Cellular Analysis(RTCA) assays were used to detect cell proliferation and growth. Transcriptome and CHIP assays were used to examine the molecular biology changes and molecular interaction in these cells. Nude mice was utilized to study the correlation of JARID1B and tumor growth in vivo.Results: Here, we first observed that JARID1B was significantly upregulated in CRC tissue compared to adjacent normal tissues. In CRC patients, JARID1B high expression was positively relation with poor overall survival. Multivariate analyses revealed that high JARID1B expression was an independent predictive marker for the poor prognosis of CRC. In addition, we found that JARID1B promoted CRC cells proliferation by Wnt/β-catenin signaling pathway. Further studies demonstrated CDX2 as a downstream target of JARID1B, and our data demonstrated that CDX2 is crucial for JARID1B -mediated Wnt/β-catenin signaling pathway. Mechanistically, we demonstrated that JARID1B regulated CDX2 expression through demethylation of H3K4me3.Conclusions: CDX2 inhibited by JARID1B-derived H3K4me3 methylation promoted cells proliferation of CRC via Wnt/β-catenin signaling pathway. Therefore, our studies provided a novel insight into the role of JARID1B in CRC cells proliferation and potential new molecular target for treating CRC.

scholarly journals Eriodictyol ameliorated cognitive dysfunction in APP/PS1 mice through inhibited ferroptosis via vitamin D receptor mediated Nrf2 activation

2021 ◽  
Author(s):  
Lin Li ◽  
Wenjun Li ◽  
Xiangru Zheng ◽  
Qinglong Liu ◽  
Qian Du ◽  
...  
Keyword(s):  
Vitamin D ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Vitamin D Receptor ◽  
Amyloid Β ◽  
Qpcr Assay ◽  
Aβ Aggregation ◽  
The Brain

Abstract Background Alzheimer's disease (AD) is the most common type of neurodegenerative disease in contemporary era, and it is still clinically incurable. Eriodictyol, a natural flavonoid compound mainly exists in citrus fruits and some Chinese herbal medicine, has been reported with its effect of anti-inflammatory, antioxidant, anti-cancer and neuroprotective effects. However, there are few studies on the anti-AD effect and molecular mechanism of eriodictyol. Methods APP/PS1 mice were treated with eriodictyol and the cognitive function of mice was assessed by behavioral tests. The level of amyloid-β (Aβ) aggregation and hyper-phosphorylation of Tau in the brain of mice were detected by histological analysis and Western blotting. Meanwhile, HT-22 cells which induced by amyloid-β peptide (1-42) (Aβ1−42) oligomer were treated with eriodictyol after which cell viability was determined and the production of p-Tau was tested by Western blotting. Then, the characteristics of ferroptosis, including iron aggregation, lipid peroxidation and the expression of glutathione peroxidase type 4(GPX4), were determined both in vivo and in vitro by Fe straining, Western blotting and qPCR assay. Additionally, the expression level of Vitamin D receptor (VDR) and the activity of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway were tested by Western blotting and qPCR assay. After that, the HT-22 cells with VDR knockout were used to explore the potential mechanisms and the relationship between VDR and Nrf2 was further assessed by coimmunoprecipitation assay and bioinformatics analysis. Results Eriodictyol obviously ameliorated cognitive deficits in APP/PS1 mice, suppressed Aβ aggregation and the phosphorylated level Tau in the brain of APP/PS1 mice. Meanwhile, eriodictyol could inhibit Tau hyper-phosphorylation and neurotoxicity in HT-22 cells induced by Aβ1−42 oligomer. Furthermore, both in vivo and in vitro, eriodictyol showed the anti-ferroptosis effect and its mechanism may connected with the activation of Nrf2/HO-1 signaling pathway. Additionally, the further experiment explains that the activation of Nrf2/HO-1 signaling pathway with eriodictyol treatment mediated by VDR. Conclusions Eriodictyol alleviated memory impairment and AD-like pathological changes via activating Nrf2/HO-1 signaling pathway mediated by VDR, which provide a new possibility for the treatment of AD.

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