6 results on '"Shaoyu Zhong"'
Search Results
2. Hepatocyte phosphatase DUSP22 mitigates NASH-HCC progression by targeting FAK
- Author
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Chenxu Ge, Jun Tan, Xianling Dai, Qin Kuang, Shaoyu Zhong, Lili Lai, Chao Yi, Yan Sun, Jing Luo, Chufeng Zhang, Liancai Zhu, Bochu Wang, and Minxuan Xu
- Subjects
Carcinoma, Hepatocellular ,Mitogen-Activated Protein Kinase 3 ,Multidisciplinary ,Liver Neoplasms ,NF-kappa B ,General Physics and Astronomy ,General Chemistry ,Lipids ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Liver ,Non-alcoholic Fatty Liver Disease ,Focal Adhesion Protein-Tyrosine Kinases ,Disease Progression ,Hepatocytes ,Animals ,Dual-Specificity Phosphatases ,Humans ,Mitogen-Activated Protein Kinase Phosphatases ,Reactive Oxygen Species - Abstract
Nonalcoholic steatohepatitis (NASH), a common clinical disease, is becoming a leading cause of hepatocellular carcinoma (HCC). Dual specificity phosphatase 22 (DUSP22, also known as JKAP or JSP-1) expressed in numerous tissues plays essential biological functions in immune responses and tumor growth. However, the effects of DUSP22 on NASH still remain unknown. Here, we find a significant decrease of DUSP22 expression in human and murine fatty liver, which is mediated by reactive oxygen species (ROS) generation. Hepatic-specific DUSP22 deletion particularly exacerbates lipid deposition, inflammatory response and fibrosis in liver, facilitating NASH and non-alcoholic fatty liver disease (NAFLD)-associated HCC progression. In contrast, transgenic over-expression, lentivirus or adeno-associated virus (AAV)-mediated DUSP22 gene therapy substantially inhibit NASH-related phenotypes and HCC development in mice. We provide mechanistic evidence that DUSP22 directly interacts with focal adhesion kinase (FAK) and restrains its phosphorylation at Tyr397 (Y397) and Y576 + Y577 residues, subsequently prohibiting downstream activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) cascades. The binding of DUSP22 to FAK and the dephosphorylation of FAK are indispensable for DUSP22-meliorated NASH progression. Collectively, our findings identify DUSP22 as a key suppressor of NASH-HCC, and underscore the DUSP22-FAK axis as a promising therapeutic target for treatment of the disease.
- Published
- 2022
3. The E3 ubiquitin-protein ligase Trim31 alleviates non-alcoholic fatty liver disease by targeting Rhbdf2 in mouse hepatocytes
- Author
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Minxuan Xu, Jun Tan, Wei Dong, Benkui Zou, Xuepeng Teng, Liancai Zhu, Chenxu Ge, Xianling Dai, Qin Kuang, Shaoyu Zhong, Lili Lai, Chao Yi, Tingting Tang, Junjie Zhao, Longyan Wang, Jin Liu, Hao Wei, Yan Sun, Qiufeng Yang, Qiang Li, Deshuai Lou, Linfeng Hu, Xi Liu, Gang Kuang, Jing Luo, Mingxin Xiong, Jing Feng, Chufeng Zhang, and Bochu Wang
- Subjects
Multidisciplinary ,Ubiquitin-Protein Ligases ,Intracellular Signaling Peptides and Proteins ,nutritional and metabolic diseases ,General Physics and Astronomy ,General Chemistry ,digestive system diseases ,General Biochemistry, Genetics and Molecular Biology ,Tripartite Motif Proteins ,Mice ,Liver ,Non-alcoholic Fatty Liver Disease ,Hepatocytes ,Animals ,Humans ,Carrier Proteins - Abstract
Systemic metabolic syndrome significantly increases the risk of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). However, no effective therapeutic strategies are available, practically because our understanding of its complicated pathogenesis is poor. Here we identify the tripartite motif-containing protein 31 (Trim31) as an endogenous inhibitor of rhomboid 5 homolog 2 (Rhbdf2), and we further determine that Trim31 directly binds to Rhbdf2 and facilitates its proteasomal degradation. Hepatocyte-specific Trim31 ablation facilitates NAFLD-associated phenotypes in mice. Inversely, transgenic or ex vivo gene therapy-mediated Trim31 gain-of-function in mice with NAFLD phenotypes virtually alleviates severe deterioration and progression of steatohepatitis. The current findings suggest that Trim31 is an endogenous inhibitor of Rhbdf2 and downstream cascades in the pathogenic process of steatohepatitis and that it may serve as a feasible therapeutical target for the treatment of NAFLD/NASH and associated metabolic disorders.
- Published
- 2022
4. Juglanin protects against high fat diet-induced renal injury by suppressing inflammation and dyslipidemia via regulating NF-κB/HDAC3 signaling
- Author
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Linfeng Hu, Shaoyu Zhong, Qin Kuang, Jun Tan, Chao Yi, Yan Sun, Qiang Li, Minxuan Xu, Chenxu Ge, Deshuai Lou, and Xianling Dai
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Cell Survival ,Immunology ,Anti-Inflammatory Agents ,Inflammation ,Diet, High-Fat ,Kidney ,Histone Deacetylases ,Cell Line ,Nephrin ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Internal medicine ,medicine ,Immunology and Allergy ,Animals ,Humans ,Glycosides ,Kaempferols ,Dyslipidemias ,Hypolipidemic Agents ,Pharmacology ,Metabolic Syndrome ,biology ,business.industry ,NF-kappa B ,Lipid metabolism ,medicine.disease ,Lipid Metabolism ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,030220 oncology & carcinogenesis ,Podocin ,biology.protein ,Kidney Diseases ,medicine.symptom ,Insulin Resistance ,business ,Dyslipidemia ,Kidney disease ,Signal Transduction - Abstract
Obesity is an important factor implicated in chronic kidney disease (CKD). Juglanin (Jug) is a natural compound extracted from the crude Polygonumaviculare, showing anti-inflammatory and anti-diabetic effects. However, whether Jug has protective effects against obesity-induced renal injury, little has been investigated. Herein, we attempted to explore the potential of Jug in mediating obesity-induced kidney disease in high fat diet (HFD)-challenged mice. Our results suggested that chronic HFD feeding markedly increased the body weights of mice compared to the ones fed with normal chow diet (NCD), along with significant glucose intolerance and insulin resistance. However, these metabolic disorders induced by HFD were effectively alleviated by Jug treatments in a dose-dependent manner. Moreover, HFD-challenged mice showed apparent histopathological changes in renal tissues with significant collagen accumulation, which were attenuated by Jug supplementation. In addition, Jug treatment decreased the expression levels of kidney injury molecule-1 (KIM-1), while increased nephrin and podocin expression levels in kidney of HFD-challenged mice, improving the renal dysfunction. Furthermore, HFD led to lipid deposition in kidney samples of mice by enhancing abnormal lipid metabolism. In addition, HFD promoted the releases of circulating pro-inflammatory cytokines, and enhanced the renal inflammation by activating nuclear factor-kappa B/histone deacetylase 3 (NF-κB/HDAC3) signaling. HFD-induced dyslipidemia and inflammation were considerably abrogated by Jug administration in mice. The protective effects of Jug against renal injury were confirmed in palmitate (PA)-stimulated HK2 cells in vitro mainly through suppressing the nuclear translocation of NF-κB and HDAC3, repressing inflammation and lipid accumulation eventually. Hence, Jug could ameliorate HFD-induced kidney injury mainly through blocking the NF-κB/HDAC3 nuclear translocation.
- Published
- 2020
5. Oral flavonoid fisetin treatment protects against prolonged high-fat-diet-induced cardiac dysfunction by regulation of multicombined signaling
- Author
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Yan Sun, Lili Lai, Jun Tan, Minxuan Xu, Jing Feng, Huanhuan Li, Jianxia Zhan, Chenxu Ge, Geng Chen, Shaoyu Zhong, Xianling Dai, Chao Yi, Qin Kuang, Tingting Tang, Mingxin Xiong, Tingting Long, Linfeng Hu, and Qiufeng Yang
- Subjects
Male ,0301 basic medicine ,Flavonols ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,030204 cardiovascular system & hematology ,Biochemistry ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Fibrosis ,Insulin ,Myocytes, Cardiac ,Metabolic Syndrome ,Nutrition and Dietetics ,Metabolic disorder ,Heart ,Echocardiography ,Tumor necrosis factor alpha ,Signal Transduction ,medicine.medical_specialty ,Heart Diseases ,Diet, High-Fat ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Molecular Biology ,Dyslipidemias ,Flavonoids ,Inflammation ,business.industry ,Myocardium ,Glucose Tolerance Test ,medicine.disease ,Rats ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,chemistry ,Insulin Resistance ,Metabolic syndrome ,business ,Dyslipidemia ,Fisetin - Abstract
Excess high-fat diet (HFD) intake predisposes the occurrence of obesity-associated heart injury, but the mechanism is elusive. Fisetin (FIS), as a natural flavonoid, has potential activities to alleviate obesity-induced metabolic syndrome. However, the underlying molecular mechanisms of FIS against HFD-induced cardiac injury remain unclear. The present study was to explore the protective effects of FIS on cardiac dysfunction in HFD-fed mice. We found that FIS alleviated HFD-triggered metabolic disorder by reducing body weight, fasting blood glucose and insulin levels, and insulin resistance. Moreover, FIS supplements significantly alleviated dyslipidemia in both mouse hearts and cardiomyocytes stimulated by metabolic stress. FIS treatment abolished HFD-induced inflammatory response in heart tissues through suppressing TNF receptor-1/TNF receptor-associated factor-2 (Tnfr-1/Traf-2) signaling. Furthermore, FIS induced a strong reduction in the expression of fibrosis-related genes, contributing to the inhibition of fibrosis by inactivating transforming growth factor (Tgf)-β1/Smads/Erk1/2 signaling. Collectively, these results demonstrated that FIS could be a promising therapeutic strategy for the treatment of obesity-associated cardiac injury.
- Published
- 2020
6. Fisetin nanoparticles protect against PM2.5 exposure-induced neuroinflammation by down-regulation of astrocytes activation related NF-κB signaling pathway
- Author
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Shaoyu Zhong, Deshuai Lou, Lili Lai, Bochu Wang, Jun Tan, Linfeng Hu, Qiang Li, Yan Sun, Minxuan Xu, Mingxin Xiong, Chao Yi, and Chenxu Ge
- Subjects
0301 basic medicine ,Antioxidant ,medicine.medical_treatment ,Medicine (miscellaneous) ,PM2.5 ,Inhibitory postsynaptic potential ,medicine.disease_cause ,NF-κB ,03 medical and health sciences ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Downregulation and upregulation ,Western blot ,medicine ,TX341-641 ,Neuroinflammation ,030109 nutrition & dietetics ,Nutrition and Dietetics ,medicine.diagnostic_test ,Nutrition. Foods and food supply ,04 agricultural and veterinary sciences ,040401 food science ,Cell biology ,chemistry ,Mechanism of action ,Fisetin nanoparticle ,medicine.symptom ,Astrocyte ,Fisetin ,Oxidative stress ,Food Science - Abstract
Astrocytes activation related NF-κB signaling and oxidative stress were treated as key target associated with PM2.5 threating nerve injury. Unfortunately, the underlying molecular mechanisms of interaction between NF-κB signaling, glial cells activation in neuroinflammation are still not absolutely explained. Fisetin, a natural flavonoid was found to be promote health, partly due to its ability in antioxidant and anti-inflammation. In this regard, we constructed fisetin nanoparticles (FN) to investigate the anti-inflammatory effect in PM2.5-induced mice. Accordingly, qPCR and western blot analysis indicated that astrocytes activation related NF-κB signaling and oxidative stress contributed to PM2.5-induced neuroinflammation, which were significantly suppressed by increasing concentration of FN treatment. Also, FN may directly enhance anti-oxidative stress and anti-inflammatory way to perform inhibitory effects on NF-κB related glial cells activation. Overall, here we identified a new mechanism of action of FN as potential anti-inflammatory product against PM2.5-induced neuroinflammation via regulation of astrocytes activation related NF-κB.
- Published
- 2020
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