Plasma Levels and Gene Expression of RANK in Non-Alcoholic Fatty Liver Disease

Hadinia, Abolghasem; Doustimotlagh, Amir Hossein; Goodarzi, Hamid Reza; Arya, Arash; Jafarinia, Mojtaba

doi:10.7754/clin.lab.2019.190913

Cited by 5 publications

(8 citation statements)

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“… 32 RANK plasma levels and peripheral blood mononuclear cell mRNA levels were also found to be decreased in NAFLD patients. 33 Similarly, the plasma OX40 level was also positively correlated with disease severity in NASH patients. OX40, a key regulator of innate and adaptive immunity in the liver, promoted NASH initiation and development by increasing the functions of proinflammatory monocytes, macrophages, and T cells.…”

Section: Nafld/nonalcoholic Steatohepatitis/aldmentioning

confidence: 91%

“…OX40, a key regulator of innate and adaptive immunity in the liver, promoted NASH initiation and development by increasing the functions of proinflammatory monocytes, macrophages, and T cells. 33 This suggests that the noncanonical NF-κB signaling pathway may have a role in the formation and development of NAFLD/NASH.…”

Section: Nafld/nonalcoholic Steatohepatitis/aldmentioning

confidence: 99%

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Noncanonical NF-κB Signaling Pathway in Liver Diseases

Chen

Zhang

2020

Journal of Clinical and Translational Hepatology

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The noncanonical NF-κB signaling pathway is an important branch of NF-κB signaling. It is involved in regulating multiple important biological processes, including inflammation and host immune response. A central adaptor protein of the noncanonical NF-κB pathway is NF-κB-inducing kinase (NIK), which activates the downstream kinase IKKα to process p100 to p52, thereby forming the RelB/p52 heterodimer to initiate the expression of target genes. Currently, many specific inhibitors and monoclonal antibodies targeting or triggering this pathway are being developed and tested for various diseases, including cancers, autoimmune diseases, and virus infection. Given that aberrant activation of the noncanonical NF-κB pathway is frequently observed in various liver diseases, targeting this pathway may be a promising therapeutic strategy to alleviate liver inflammation. Moreover, activation of this pathway may contribute to the antiviral immune response and promote the clearance of persistent hepatotropic virus infection. Here, we review the role of the noncanonical NF-κB pathway in the occurrence and development of different liver diseases, and discuss the potency and application of modulating the noncanonical NF-κB pathway for treatment of these liver diseases.

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Section: Nafld/nonalcoholic Steatohepatitis/aldmentioning

confidence: 91%

Section: Nafld/nonalcoholic Steatohepatitis/aldmentioning

confidence: 99%

Noncanonical NF-κB Signaling Pathway in Liver Diseases

Chen

Zhang

2020

Journal of Clinical and Translational Hepatology

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“…Twentyfive healthy men with normal liver ultrasonography and normal liver function tests were used as a control group. The patients were formerly involved in our studies on RANK and NAFLD, and some of their data have been used in a recent publication [25]. Individuals who did not have the following criteria were comprised in the study: history of liver diseases for instance cirrhosis, hepatitis, and cancer, smoking and alcohol, thyroid and parathyroid disorders, history of taking medications that affect the bone marrow, such as interferon, corticosteroids, statin anticoagulants, hormone therapy, calcitonin-bisphosphonate, antidepressants, and thyroxin.…”

Section: Study Populationmentioning

confidence: 99%

“…Body mass index (BMI) for all individuals was calculated (body weight (kg)/square of the individual's height (m2)). Waist circumference, hip circumference, as well as waist to hip ratio (WHR) were determined, as described previously (published data) [25]. Venous blood samples were taken from the study participants after an overnight fast.…”

Section: Biochemical and Anthropometric Featuresmentioning

confidence: 99%

“…Venous blood samples were taken from the study participants after an overnight fast. Fasting blood glucose (FBG), lipid profile, and fasting plasma insulin was measured as previously described [25]. Homeostasis model assessment of insulin resistance (HOMA-IR) was used for determining of insulin resistance by this equation: [FBG (mg/dL)] × [fasting plasma insulin (μU/mL)]/405 [26].…”

Section: Biochemical and Anthropometric Featuresmentioning

confidence: 99%

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Circulating mRNA and plasma levels of osteoprotegerin and receptor activator of NF‐κB ligand in nonalcoholic fatty liver disease

Nikseresht

Azarmehr

Arya

et al. 2020

Biotechnology and Applied Biochemistry

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Pathogenesis of the beginning and progression of nonalcoholic fatty liver disease (NAFLD) has not been clarified exactly. The osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis seems to play an imperative function in the onset and progression of this disease. The goal of the present study was to investigate the peripheral blood mononuclear cell (PBMC) expression and plasma levels of RANKL and OPG cytokines in NAFLD patients and compare them with healthy group. Plasma levels of OPG and RANKL were determined with ELISA kits in 57 men with NAFLD and 25 healthy men as controls. Biochemical and anthropometric parameters tests were also evaluated in the study groups. RANKL and OPG mRNA contents were evaluated by quantitative RT-PCR. OPG contents were markedly decreased in NAFLD patients as compared with healthy patients [1.43 (1.05-5.45)] versus [2.94 (1.76-4.73)] ng/mL; P = 0.007). The levels of RANKL were significantly reduced in NAFLD patients [74.00 (56.26-203.52) ng/mL] than in healthy patients [119.37 (83.71-150.13) ng/mL]; (P = 0.03). Also, OPG and RANKL gene expression were significantly decreased in NAFLD patients in comparison with the control group (P < 0.05). Moreover, receiver operating characteristic curve indicated that OPG may have a good capability to discriminate between NAFLD patients and normal individuals. A positive correlation was observed between OPG and RANKL in plasma sample (r = 0.495) (P = 0.000). Decreased plasma levels and gene expression of RANKL and OPG cytokines in NAFLD patients indicate that there is a relationship between these cytokines and the pathology of NAFLD disease. Confirmation of this association as well as the mechanism and role of these cytokines in NAFLD require further studies.

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Osteoprotegerin/Receptor Activator of Nuclear Factor-Kappa B Ligand/Receptor Activator of Nuclear Factor-Kappa B Axis in Obesity, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease

Vachliotis

Polyzos

2023

Curr Obes Rep

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Purpose of Review To summarize evidence on the potential involvement of the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B (NF-κΒ) ligand (RANKL)/receptor activator of NF-κΒ (RANK) axis in the pathogenesis of metabolic diseases. Recent Findings The OPG-RANKL-RANK axis, which has been originally involved in bone remodeling and osteoporosis, is now recognized as a potential contributor in the pathogenesis of obesity and its associated comorbidities, i.e., type 2 diabetes mellitus and nonalcoholic fatty liver disease. Besides bone, OPG and RANKL are also produced in adipose tissue and may be involved in the inflammatory process associated with obesity. Metabolically healthy obesity has been associated with lower circulating OPG concentrations, possibly representing a counteracting mechanism, while elevated serum OPG levels may reflect an increased risk of metabolic dysfunction or cardiovascular disease. OPG and RANKL have been also proposed as potential regulators of glucose metabolism and are potentially involved in the pathogenesis of type 2 diabetes mellitus. In clinical terms, type 2 diabetes mellitus has been consistently associated with increased serum OPG concentrations. With regard to nonalcoholic fatty liver disease, experimental data suggest a potential contribution of OPG and RANKL in hepatic steatosis, inflammation, and fibrosis; however, most clinical studies showed reduction in serum concentrations of OPG and RANKL. Summary The emerging contribution of the OPG-RANKL-RANK axis to the pathogenesis of obesity and its associated comorbidities warrants further investigation by mechanistic studies and may have potential diagnostic and therapeutic implications.

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Plasma Levels and Gene Expression of RANK in Non-Alcoholic Fatty Liver Disease

Cited by 5 publications

References 0 publications

Noncanonical NF-κB Signaling Pathway in Liver Diseases

Noncanonical NF-κB Signaling Pathway in Liver Diseases

Circulating mRNA and plasma levels of osteoprotegerin and receptor activator of NF‐κB ligand in nonalcoholic fatty liver disease

Osteoprotegerin/Receptor Activator of Nuclear Factor-Kappa B Ligand/Receptor Activator of Nuclear Factor-Kappa B Axis in Obesity, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease

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