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Hypoxia induces production of citrullinated proteins in human fibroblast‐like synoviocytes through regulating HIF 1α
Author(s) -
Yu R.,
Li C.,
Sun L.,
Jian L.,
Ma Z.,
Zhao J.,
Liu X.
Publication year - 2018
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12654
Subject(s) - citrullination , hypoxia (environmental) , pathogenesis , cancer research , hypoxia inducible factors , rheumatoid arthritis , immunology , medicine , microbiology and biotechnology , citrulline , biology , chemistry , gene , arginine , biochemistry , organic chemistry , amino acid , oxygen
Hypoxia is a prominent microenvironment feature in a range of disorders including cancer, rheumatoid arthritis ( RA ), atherosclerosis, inflammatory bowel disease ( IBD ), infection and obesity. Hypoxia promotes biological functions of fibroblast‐like synoviocytes via regulating hypoxia‐inducible factor 1α ( HIF 1α). Dysregulated protein citrullination in RA drives the production of antibodies to citrullinated proteins, a highly specific biomarker of RA . However, the mechanisms promoting citrullination in RA are not yet fully elucidated. In this study, we investigated whether pathophysiological hypoxia as found in the rheumatoid synovium modulates the citrullination in human fibroblast‐like synoviocytes ( HFLS ). Here, we found that peptidylarginine deiminase 2 ( PAD 2) and citrullinated proteins were increased in HFLS after exposure to hypoxia. Moreover, knocking down HIF 1α by HIF 1α si RNA ameliorated the expression of PAD 2 and citrullinated proteins. Collectively, this study provides a new mechanism involved in generating citrullinated proteins: hypoxia promotes citrullination and PAD production in HFLS . Concurrently, we also proposed a novel hypoxia involved mechanism in RA pathogenesis. This study deepens our understanding of the role of hypoxia in the pathogenesis of RA and provides a potential therapeutic strategy for RA .