SOCS2 Suppresses Inflammation and Apoptosis During NASH Progression Through Limiting NF-κB Activation in Macrophages

Autor: Xiaoying Zhou, Zhongming Tan, Shuo Li, Guoxin Zhang, Tingting Yu, Kangpeng Jin, Sheng Han, Han Chen
Rok vydání: 2021
Předmět:
medicine.medical_treatment
Suppressor of Cytokine Signaling Proteins
Inflammation
Fatty Acids
Nonesterified
Diet
High-Fat
Applied Microbiology and Biotechnology
digestive system
Suppressor of cytokine signaling 2
NF-κB
Mice
chemistry.chemical_compound
Non-alcoholic Fatty Liver Disease
Stress
Physiological
Animals
Humans
Medicine
Nonalcoholic steatohepatitis
Molecular Biology
SOCS2
Ecology
Evolution
Behavior and Systematics
Bone Marrow Transplantation
business.industry
Macrophages
apoptosis
NF-kappa B
nutritional and metabolic diseases
Inflammasome
Cell Biology
medicine.disease
digestive system diseases
RAW 264.7 Cells
Cytokine
Gene Expression Regulation
chemistry
Apoptosis
Gene Knockdown Techniques
Cancer research
Sample collection
Steatosis
medicine.symptom
Signal transduction
business
Developmental Biology
Research Paper
Signal Transduction
medicine.drug
Zdroj: International Journal of Biological Sciences
ISSN: 1556-5068
DOI: 10.2139/ssrn.3777148
Popis: Background: Inflammation and apoptosis play a crucial role in the progression of nonalcoholic steatohepatitis (NASH). Suppressor of cytokine signaling 2 (SOCS2) is one of classic negative regulators of cytokine signaling, which has recently been described as anti-inflammatory mediators. However, the role of SOCS2 in macrophages during NASH progression and the relationship among SOCS2, inflammation, apoptosis and NASH is largely unknown. Herein, we aimed to study the function of SOCS2 in NASH progression. Methods: We detected SOCS2 expression in macrophages in human subjects without steatosis, with simple steatosis and with NASH to confirm the relationship between SOCS2 and NASH. Free fatty acids was used to establish stress environment in RAW cell lines stably overexpressing or knockdown SOCS2. In vitro and vivo assays also performed to study the molecular function of SOCS2 in NASH progression. Findings: Our human samples and NASH model in vitro illustrated that SOCS2 is decreased in macrophages during NASH progression and is negatively correlated to NASH level. Meanwhile, In vitro assays show SOCS2 overexpression in macrophages suppresses inflammation and apoptosis via inhibiting NF-κB signaling pathway, while SOCS2 knock-down in macrophages caused an increased activation of NF-κB, which can be blocked by ammonium 1-pyrrolidinedithiocarbamate (PDTC). In addition SOCS2 in macrophages also suppresses inflammation via limiting the activation of inflammasomes. Consist with these, our BMT model also confirm the SOCS2 function in macrophages during NASH. Interpretation: Our data strongly indicate that SOCS2 plays a inhibitor of inflammation and apoptosis via NF-κB signal pathway and inflammasome signal pathway in macrophages during NASH. Further studies are required to explore the potential prevention and therapeutic strategies of SOCS2 for this common liver disease. Funding Statement: This work was supported by the National Natural Science Foundation of China (Nos. 81970499 and 81770561), Jiangsu Medical Leading Talent, Innovation Team (No. CXTDA2017033), and Jiangsu Province “333” project (No. BRA2014332) and National Natural Science Foundation of China (Nos. 81972675). Declaration of Interests: The authors declare no conflict of interest relevant to the present manuscript. Ethics Approval Statement: All procedures that involved human sample collection were approved by the tissue bank of The Affiliated Drum Tower Hospital, Nanjing University (Nanjing, China). Informed consent for gene expression analysis of tissue was obtained from each patient before surgery, and the study was approved by our institutional ethics committee. The ethics committe of the Institutional Animal Care and Use Committee (IACUC). First Affiliated Hospital of Nanjing Medical University approved this study, (Ethics Number: 2018-SRFA-034).
Databáze: OpenAIRE
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