Hypoxia induces production of citrullinated proteins in human fibroblast-like synoviocytes through regulating HIF1α

Scandinavian Journal of Immunology
R YuX Liu

Abstract

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 (HIF1α). 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 (PAD2) and citrullinated proteins were increased in HFLS after exposure to hypoxia. Moreover, knocking down HIF1α by HIF1α siRNA ameliorated the expression of PAD2 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...Continue Reading

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Citations

Feb 23, 2020·International Journal of Molecular Sciences·Miguel Beato, Priyanka Sharma
Jan 4, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Zhenzhen MaXiangyuan Liu
Mar 3, 2020·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Bergljót MagnadóttirSigrun Lange
May 7, 2021·Frontiers in Pharmacology·Hongxing WangXiaotian Chang
Sep 24, 2020·Journal of Proteome Research·Rui VitorinoJennifer E Van Eyk
Jan 1, 2022·Cellular and Molecular Life Sciences : CMLS·Mohammed AlghamdiElrashdy M Redwan

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