CCCTC-binding factor: the specific transcription factor of β-galactoside α-2,6-sialyltransferase 1 that upregulates the sialylation of anti-citrullinated protein antibodies in rheumatoid arthritis.

Autor:	Zhao H; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.; Institute of Autoimmune Diseases, Wenzhou Medical University, Wenzhou, Zhejiang, China., Wang H; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.; Institute of Autoimmune Diseases, Wenzhou Medical University, Wenzhou, Zhejiang, China., Qin Y; Institute of Autoimmune Diseases, Wenzhou Medical University, Wenzhou, Zhejiang, China., Ling S; Institute of Autoimmune Diseases, Wenzhou Medical University, Wenzhou, Zhejiang, China., Zhai H; Institute of Autoimmune Diseases, Wenzhou Medical University, Wenzhou, Zhejiang, China., Jin J; Institute of Autoimmune Diseases, Wenzhou Medical University, Wenzhou, Zhejiang, China.; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China., Fang L; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.; Institute of Autoimmune Diseases, Wenzhou Medical University, Wenzhou, Zhejiang, China., Cao Z; Institute of Autoimmune Diseases, Wenzhou Medical University, Wenzhou, Zhejiang, China., Jin S; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China., Yang X; Institute of Autoimmune Diseases, Wenzhou Medical University, Wenzhou, Zhejiang, China.; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China., Wang J; Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.; Institute of Autoimmune Diseases, Wenzhou Medical University, Wenzhou, Zhejiang, China.; Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Mar 01; Vol. 63 (3), pp. 826-836.
DOI:	10.1093/rheumatology/kead282
Abstrakt:	Objective: Sialylation of the crystallizable fragment (Fc) of ACPAs, which is catalysed by β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) could attenuate inflammation of RA. In this study, we screened the transcription factor of ST6GAL1 and elucidated the mechanism of transcriptionally upregulating sialylation of ACPAs in B cells to explore its role in the progression of RA. Methods: Transcription factors interacting with the P2 promoter of ST6GAL1 were screened by DNA pull-down and liquid chromatography with tandem mass spectrometry (LC-MS/MS), and verified by chromatin immunoprecipitation (ChIP), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The function of the CCCTC-binding factor (CTCF) on the expression of ST6GAL1 and the inflammatory effect of ACPAs were verified by knocking down and overexpressing CTCF in B cells. The CIA model was constructed from B cell-specific CTCF knockout mice to explore the effect of CTCF on arthritis progression. Results: We observed that the levels of ST6GAL1 and ACPAs sialylation decreased in the serum of RA patients and were negatively correlated with DAS28 scores. Subsequently, CTCF was screened and verified as the transcription factor interacting with the P2 promoter of ST6GAL1, which enhances the sialylation of ACPAs, thus weakening the inflammatory activity of ACPAs. Furthermore, the above results were also verified in the CIA model constructed from B cell-specific CTCF knockout mice. Conclusion: CCCTC-binding factor is the specific transcription factor of β-galactoside α-2,6-sialyltransferase 1 in B cells that upregulates the sialylation of ACPAs in RA and attenuates the disease progression. (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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