Tristetraprolin Gene Single-Nucleotide Polymorphisms and mRNA Level in Patients With Rheumatoid Arthritis

Yang, Xiao‐Ke; Chen, Bin; Zhang, Mingyue; Xu, Shengqian; Shuai, Zongwen

doi:10.3389/fphar.2021.728015

Cited by 5 publications

(4 citation statements)

References 33 publications

(35 reference statements)

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“…Given its ability to target and reduce the mRNA levels of several in ammatory cytokines, including TNF-a, it is generally considered to play a crucial function in the development of RA pathology (31). This nding is supported by the research of Yang et al (32), whose study reported decreased levels of TTP mRNA in PBMCs collected from patients with RA. Additionally, the authors identi ed an association between a SNP (rs3746083) located in the gene encoding for TTP and RA susceptibility in Chinese RA patients.…”

Section: Discussionmentioning

confidence: 91%

Mapping the Regulatory Programs of RNA Binding Protein Regulators in Rheumatoid Arthritis: Data from Single-Cell Transcriptome Analysis

Luo

Lin

Wei

et al. 2023

Preprint

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Background RNA binding proteins (RBPs), especially cell-specific RBPs are involved in critical processes such as alternative splicing of messenger RNAs and translational control, leading to the expression of cell-specific functional proteins. However, the expression pattern of RBPs in different cells of rheumatoid arthritis and their associated aberrant regulation remain largely unexplored.Methods We collected 2141 RNA binding protein genes (RBPs) from literature and identified cell populations present in rheumatoid arthritis and osteoarthritis control samples using single-cell data. We compared the changes in the relative proportions of cell classes between them and analyzed RBP expression patterns specific to different cell types. We investigated fibroblast cell populations and their cellular communication with different immune cells. Additionally, we used bulk RNA-seq data from rheumatoid arthritis and osteoarthritis samples to identify highly conserved variable splicing events and established a co-variation network of RBPs and these splicing events.Results We observed a greater number of down-regulated RBPs in each cell type, except for fibroblasts, endothelial cells, and macrophages, where the number of up-regulated genes was much higher. In fibroblasts from RA and OA patients, we identified 105 upregulated RBPs and 133 downregulated RBPs. These RBPs were co-expressed with genes enriched in various functional pathways, including extracellular matrix organization, cell adhesion, collagen fibril organization, and cytokine signaling. Cellular communication analysis demonstrated enhanced signaling pathways, like CXCL12-CXCR4, between fibroblasts and macrophages in RA. We identified a total of 715 differentially variable splicing events in our study, and alternative 5' and 3' splicing were the most prevalent. Some RBPs, such as MBNL2 in endothelial cells and U2AF1, SF3B6, and SF3B14 in fibroblast cells, may play a role in the pathogenesis of RA through splicing regulation.Conclusion In this study, we analyzed single-cell datasets to identify the inherent characteristics and abnormal expression patterns of RBPs in different cell types of patients with RA. Our findings revealed that certain cell-specific RBPs were associated with inflammatory signaling pathways and splicing regulation in RA. These findings suggest that the dysregulation of RBPs may contribute to the development of RA and highlight potential pathways for therapeutic interventions.

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Section: Discussionmentioning

confidence: 91%

Mapping the Regulatory Programs of RNA Binding Protein Regulators in Rheumatoid Arthritis: Data from Single-Cell Transcriptome Analysis

Luo

Lin

Wei

et al. 2023

Preprint

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“…A recent study by Yang et al [14] was "the first study to prove that TTP dysregulation might be related to the pathogenesis and development of Rheumatoid arthritis (RA), and the polymorphism of the TTP gene may be protective of RA in a Chinese population. They suggested that TTP might be involved in the regulation of autoimmune diseases".…”

Section: Discussionmentioning

confidence: 99%

Role of Tristetraprolin in Psoriasis: A Case Control Study

El-agamy¹,

Keshk²,

Fawzy³

et al. 2022

JAMMR

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Background: Tristetraprolin (TTP) is RNA-binding protein encoded by Zfp36 gene which regulates the mRNA stability of several important cytokines. Due to its critical role in control of inflammation, TTP deficiency leads to the spontaneous development of a complex inflammatory syndrome. So far, this phenotype has been largely attributed to dysregulated production of TNF and IL23 by myeloid cells, such as macrophages or DCs. The expression of TTP was studied in keratinocytes and explored its role in the imiquimod-induced psoriasis model. Objective: To study the possible role of Tristetraprolin in the pathogenesis of psoriasis. Methods: The study included 32 patients who were randomly assigned to two groups, group 1 included 22 patients with psoriasis and group 2 included 10 apparently healthy individual as a control group. Skin specimens were obtained by punch biopsy (3mm) from the skin lesion of the patients and normal skin of controls. Skin tissue from each case was homogenized in phosphate buffer saline (pH 7.4). The crude homogenate was centrifuged, and the resultant supernatant was removed and used for the measurement of Tristetraprolin level by ELISA. Results: Regarding to Tristetraprolin (ng/m protein) level, there was a significant difference between cases and control group regarding skin tissue TTP level. TTP was significantly lower in psoriasis patient when compared to controls (P value < 0.001). As regard relation between the level of TTP and the disease severity represented as PASI score; there was significant difference in TTP level between different grades (P value 0.001) with the lowest level in cases with severe psoriasis. Conclusions: Tristetraprolin may play a role in pathogenesis of psoriasis and may provide important clues to assist in the development of new therapeutic strategies for psoriatic patients.

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“…ICAM-1 (along with VCAM-1) is involved in multiple mechanisms that promote inflammation, predominantly by promoting local infiltration of inflammatory cells (Klimiuk et al, 2002). Supporting the relevance of TTP in RA, Yang et al reported a reduction of TTP mRNA in human PBMCs purified from RA patients and an association between a SNP located in the gene encoding for TTP (rs3746083) and RA predisposition in Chinese RA patients (Yang et al, 2021).…”

Section: Rbps and Rheumatoid Arthritismentioning

confidence: 99%

RNA‐binding proteins in autoimmunity: From genetics to molecular biology

et al. 2023

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Autoimmune diseases (ADs) are chronic pathologies generated by the loss of immune tolerance to the body's own cells and tissues. There is growing recognition that RNA-binding proteins (RBPs) critically govern immunity in healthy and pathological conditions by modulating gene expression posttranscriptionally at all levels: nuclear mRNA splicing and modification, export to the cytoplasm, as well as cytoplasmic mRNA transport, storage, editing, stability, and translation. Despite enormous efforts to identify new therapies for ADs, definitive solutions are not yet available in many instances. Recognizing that many ADs have a strong genetic component, we have explored connections between the molecular biology and the genetics of RBPs in ADs. Here, we review the genetics and molecular biology of RBPs in four major ADs, multiple sclerosis (MS), type 1 diabetes mellitus (T1D), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). We anticipate that gaining insights into the genetics and biology of ADs can facilitate the discovery of new therapies.

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Tristetraprolin Gene Single-Nucleotide Polymorphisms and mRNA Level in Patients With Rheumatoid Arthritis

Cited by 5 publications

References 33 publications

Mapping the Regulatory Programs of RNA Binding Protein Regulators in Rheumatoid Arthritis: Data from Single-Cell Transcriptome Analysis

Mapping the Regulatory Programs of RNA Binding Protein Regulators in Rheumatoid Arthritis: Data from Single-Cell Transcriptome Analysis

Role of Tristetraprolin in Psoriasis: A Case Control Study

RNA‐binding proteins in autoimmunity: From genetics to molecular biology

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