Genetic and epigenetic alterations of <i>cyclic AMP response element modulator</i> in rheumatoid arthritis

Tseng, Chia‐Chun; Lin, Yuan‐Zhao; Lin, Chia‐Hui; Hwang, Daw-Yang; Li, Ruei‐Nian; Tsai, Wen‐Chan; Ou, Tsan‐Teng; Wu, Chuan-Chun; Lin, Yu-Chih; Sung, Wan‐Yu; Chen, Kuan‐Yu; Chang, Shun‐Jen; Yen, Jeng-Hsien

doi:10.1111/eci.13715

Cited by 2 publications

(2 citation statements)

References 55 publications

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“…Also, CREM impacts T-cell activity in homeostasis and participates in the regulation of NF/κB signaling pathway ( 38 ). In addition to its role in inflammation and autoimmune diseases, Taiwanese scholars found that CREM expression was increased in patients with rheumatoid arthritis and its variants were involved in the progression of the disease ( 39 ). Single-cell sequencing studies showed that CREM regulons were most active in preosteoblast-S1 ( 40 ), implying that CREM variants are engaged in osteogenesis and bone homeostasis.…”

Section: Discussionmentioning

confidence: 99%

The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization

Chen

Gao

et al. 2023

Front. Immunol.

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BackgroundMany existing studies indicated that patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), tend to have the risk of low total body bone mineral density (BMD), and are more likely to have osteoporosis (OS). To determine the causal relationship between IBD and bone metabolic disorders, we herein performed a two-sample Mendelian randomization analysis (TSMR) using publicly available summary statistics.MethodsSummary statistics of total body BMD, OS and IBD were downloaded from the Open Genome-Wide Association Study (GWAS), FinnGen consortium and International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The European and East Asian populations have consisted in this Mendelian Randomization (MR) work. A range of quality control procedures were taken to select eligible instrument SNPs closely associated with total body BMD, OS and IBD. To make the conclusions more reliable, we applied five robust analytical methods, among which the inverse variance weighting (IVW) method acted as the major method. Besides, heterogeneity, pleiotropy and sensitivity were evaluated.ResultsIn the European population, the genetic association of UC on total body BMD (OR=0.97, 95%CI=0.96,0.99, P<0.001) and overall IBD on total body BMD (OR=0.98, 95%CI=0.97,1.00, P=0.013) were significant, while the effect of CD on total body BMD was not significant enough (OR=0.99, 95%CI=0.98,1.00, P=0.085). All of UC, CD and overall IBD can be the genetic risk factor of having OS with pathological fracture (UC: OR=1.13, 95%CI=1.02,1.26, P=0.024, CD: OR=1.14, 95%CI=1.05,1.25, P=0.003, overall IBD: OR=1.13, 95%CI=1.02,1.24, P=0.015). In East Asian groups, only CD had a causal relationship with OS (OR=1.04, 95% CI=1.01,1.07, P=0.019).ConclusionOur study revealed genetically predicted associations between IBD on total body BMD and OS in European and East Asian populations. This work supplemented the results of previous retrospective studies and demonstrated the necessity of BMD monitoring in patients with IBD.

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Section: Discussionmentioning

confidence: 99%

The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization

Chen

Gao

et al. 2023

Front. Immunol.

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“…Among them, we found that CREM expression was upregulated in peripheral blood. Targeted bisulphite sequencing and reverse transcription-PCR experiments revealed that the CREM promoter was hypomethylated, and the expression of CREM was upregulated in RA [ 51 ]. The CREM is a cAMP-controlled transcription factor closely associated with the regulation of the immune system.…”

Section: Discussionmentioning

confidence: 99%

Analyzation of the Peripheral Blood Mononuclear Cells Atlas and Cell Communication of Rheumatoid Arthritis Patients Based on Single-Cell RNA-Seq

Song

Zhang

Zhao

et al. 2023

Journal of Immunology Research

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Background. Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease with a multifactorial etiology. Peripheral blood is the main channel of the immune system, and peripheral blood mononuclear cells (PBMCs) are the immune cells that initiate the autoimmune inflammatory process. However, there are few reports on the mechanisms of peripheral blood immunity in RA. Methods. ScRNA-seq was performed on four RA samples and integrated with single-cell transcriptome data from four healthy control samples downloaded from publicly available databases for analysis. Results. A total of 52,073 cells were used for descending clustering analysis to map RA peripheral blood immune cells at single-cell resolution. Redimensional clustering analysis of four major immune cells (T cells, monocytes, B cells, and natural killer cells) revealed that double-negative T (DNT) cells were significantly altered in abundance and function. And a number of genes (including SOCS3, cAMP-responsive element modulator (CREM), B2M, MTFP1, RSRP1, and YWHAB) were specifically downregulated in DNT cells. RA T cells, especially DNT cells, exhibit significant metabolic defects and dysfunction, mainly in the form of inhibition of oxidative phosphorylation, ATP synthesis, and major histocompatibility complex (MHC)-I-mediated antigen presentation. In addition, cellular communication networks were established, and it was evident that RA is significantly attenuated in the number and intensity of cellular communication. Monocytes and T cells play key roles in the process of the immune inflammatory response through CCL and MHC-related pathways. Conclusions. This study describes the landscape of the peripheral blood immune system and cell communication in RA, characterizes the abundance of PBMCs, gene expression profiles, and changes in signaling pathways in RA patients, and identifies several key cell subpopulations (DNT and classic monocytes) and specific genes (SOCS3, CREM, B2M, MTFP1, RSRP1, and YWHAB). Meanwhile, we propose that classic monocytes in peripheral blood may migrate to sites of inflammation in synovial tissue under the chemotaxis of the chemokines CCL3 and CCL3L1, differentiate into macrophages, secrete proinflammatory cytokines, and thus participate in the inflammatory response. These findings provide new insights for the future elucidation of the peripheral blood immune mechanisms of RA and the search for new clinical therapeutic targets.

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Genetic and epigenetic alterations of cyclic AMP response element modulator in rheumatoid arthritis

Cited by 2 publications

References 55 publications

The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization

The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization

Analyzation of the Peripheral Blood Mononuclear Cells Atlas and Cell Communication of Rheumatoid Arthritis Patients Based on Single-Cell RNA-Seq

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