Role of glucose metabolism in aggressive phenotype of fibroblast-like synoviocytes: Latest evidence and therapeutic approaches in rheumatoid arthritis

Masoumi, M and Mehrabzadeh, M and Mahmoudzehi, S and Mousavi, M.J and Jamalzehi, S and Sahebkar, A and Karami, J (2020) Role of glucose metabolism in aggressive phenotype of fibroblast-like synoviocytes: Latest evidence and therapeutic approaches in rheumatoid arthritis. International Immunopharmacology, 89 (Part A). ISSN 15675769

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Abstract

Glucose metabolism is considerably increased in inflamed joints of rheumatoid arthritis (RA) patients at early stages. Fibroblast-like synoviocytes (FLSs) activation and subsequent joint damage are linked with metabolic alterations, especially glucose metabolism. It has been shown that glucose metabolism is elevated in aggressive phenotype of FLS cells. In this regard, glycolytic blockers are able to reduce aggressiveness of the FLS cells resulting in decreased joint damage in various arthritis models. Besides, metabolic changes in immune and non-immune cells such as FLS can provide important targets for therapeutic intervention. Glycolytic enzymes such as hexokinase 2 (HK2), phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB), and phosphoglycerate kinase (PGK) play essential roles in aggressive behavior of FLS cells. It has been documented that the HK2 enzyme is significantly upregulated in RA FLS cells, compared with osteoarthritis (OA) FLS cells. The HK2 is expressed in a few tissues and upregulated in the inflamed synovium of RA patients that makes it a potential target for RA treatment. Furthermore, HK2 has different roles in each cellular compartment, which offers another level of specificity and provides a specific target to reduce deleterious effects of inhibiting the enzyme in RA without affecting glycolysis in normal cells. Thus, targeting the HK2 enzyme might be an attractive potential selective target for arthritis therapy and safer than global glycolysis inhibition. Therefore, this review was aimed to summarize the current knowledge about glucose metabolism of FLS cells and suggest novel biomarkers, which are potential candidates for RA treatment.

Item Type: Article
Uncontrolled Keywords: Fibroblast-Like Synoviocytes (FLS) Glucose metabolism Glycolysis Hexokinase-2 (HK2)Rheumatoid Arthritis (RA)
Subjects: QW Microbiology and Immunology
Divisions: Faculty of Medicin > Department of Immunology and Allergy
Depositing User: خدیجه شبانکاره
Date Deposited: 26 Dec 2020 08:17
Last Modified: 26 Dec 2020 08:17
URI: http://eprints.bpums.ac.ir/id/eprint/9137

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