Review
Immunology
Zewen Wu, Dan Ma, Helin Yang, Jinfang Gao, Gailian Zhang, Ke Xu, Liyun Zhang
Summary: Fibroblast-like synoviocytes (FLS) play a crucial role in the pathophysiology of rheumatoid arthritis (RA) and have become the main focus of research. Advances in technology, such as high-throughput sequencing, have made it possible to identify different FLS subsets, allowing for a detailed study of RA pathogenesis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Immunology
Yanping Luo, Yunxuan Lei, Xin Guo, Dehao Zhu, Haiyang Zhang, Zizhen Guo, Zichong Xu, Hanqing Zhao, Yebin Xi, Xiaochun Peng, Lianbo Xiao, Zhaojun Wang, Xiaoyin Niu, Guangjie Chen
Summary: Fibroblast-like synoviocytes (FLS) play important roles in the pathological processes of rheumatoid arthritis (RA). CK2, elevated in RA FLS, was found to be associated with abnormal phenotypes. Targeted inhibition of CK2 using CX-4945 suppressed RA FLS proliferation, migration, and invasion, and reduced inflammation-related factors secretion. Further investigation revealed that CX-4945 can alleviate the severity of RA by modulating the p53 signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yuan Liu, Peishi Rao, Hongyan Qian, Yesi Shi, Shiju Chen, Jingying Lan, Dan Mu, Rongjuan Chen, Xinwei Zhang, Chaoqiong Deng, Gang Liu, Guixiu Shi
Summary: Fibroblast-like synoviocytes (FLS) are the main cell component in inflamed joints of patients with rheumatoid arthritis (RA) and interact with infiltrating T cells. Under normal conditions, FLS have inhibitory effects on T cells, but in RA, FLS exhibit a proinflammatory phenotype. The signals that control FLS heterogeneity are still unclear.
Article
Immunology
Xinpeng Zhou, Duoli Xie, Jie Huang, Aiping Lu, Rongsheng Wang, Yehua Jin, Runrun Zhang, Cen Chang, Lingxia Xu, Linshuai Xu, Junyu Fan, Chao Liang, Dongyi He
Summary: The study found that LLDT-8 inhibited the proliferation, invasion, and cytokine production of RA FLS by regulating the WAKMAR2/miR-4478/E2F1/p53 axis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xiao-Feng Li, Sha Wu, Qi Yan, Yuan-Yuan Wu, He Chen, Su-Qin Yin, Xin Chen, Hua Wang, Jun Li
Summary: The study reveals that PTEN methylation promotes inflammation and activation in fibroblast-like synoviocytes (FLS) in the pathogenesis of rheumatoid arthritis (RA). Inhibiting methylation can reduce inflammation and alleviate joint swelling, potentially serving as an effective treatment strategy for RA.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Weihong Xu, Lu Ye, Huaxiang Wu
Summary: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with increasing incidence globally. The study revealed that miR-4423-3p is downregulated in RA patients and targets MMP13 to inhibit cell proliferation, migration, and invasion while promoting apoptosis in HFLS-RA cells.
Article
Oncology
Jian Chen, Xian Lin, Juan He, Dandan Liu, Lianhua He, Miaomiao Zhang, Huijie Luan, Yiping Hu, Cheng Tao, Qingwen Wang
Summary: The study found that ATT has potential therapeutic effects on RA by suppressing proliferation, migration, and invasion of RA-FLSs, as well as inducing apoptosis. ATT achieves therapeutic potential for RA by modulating the METTL3/ICAM2/PI3K/AKT/p300 feedback loop.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Mehrnoosh Adib, Mahdi Taghadosi, Mohammad Naghi Tahmasebi, Arash Sharafat Vaziri, Ahmadreza Jamshidi, Mahdi Mahmoudi, Elham Farhadi
Summary: This study investigates the effects of PRIMA-1(MET) on apoptosis induction and inhibition of pro-inflammatory cytokines in fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA). The results show that PRIMA-1(MET) induces apoptosis in RA-FLSs, upregulates Noxa expression, and downregulates IL-6, IL-1β, p53, and phospho-IKBa expression. Furthermore, PRIMA-1(MET) treatment suppresses pro-inflammatory cytokine production and inhibits NF-kappa B activity. Therefore, PRIMA-1(MET) could be considered as a new therapeutic strategy for rheumatoid arthritis.
INFLAMMOPHARMACOLOGY
(2023)
Article
Immunology
Yanhua Zuo, Huaheng Xu, Yanxia Li, Zongfang Zhang, Ran Tao, Manxiang Wang
Summary: Synovial samples from RA patients and normal controls were used to isolate FLSs. Increased expression of circ_0007707 was observed in synovial samples from RA patients and FLS-RA cells. Circ_0007707 silencing inhibited cell proliferation, induced cell apoptosis, and decreased cell inflammatory response in FLS-RA cells. Mechanistically, circ_0007707 mediated cell apoptosis and inflammatory response in FLS-RA cells through the miR-27b-3p/PDE3B axis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yu Tai, Bei Huang, Pai-pai Guo, Zhen Wang, Zheng-wei Zhou, Man-man Wang, Han-fei Sun, Yong Hu, Sheng-lin Xu, Ling-ling Zhang, Qing-tong Wang, Wei Wei
Summary: Our study demonstrates the impact of TNF-alpha on cAMP homeostasis and the interaction between TNF-alpha and EP4 signaling, revealing the potential role of TRAF2 and GRK2 in the treatment of inflammatory diseases. The findings provide valuable insights into a novel form of cross-talk between cytokine receptors and G protein-coupled receptors, suggesting TRAF2-GRK2 interaction as a potential new drug target.
ACTA PHARMACOLOGICA SINICA
(2022)
Review
Immunology
Zihan Wang, Jinping Wang, Tianyi Lan, Liubo Zhang, Zeran Yan, Nan Zhang, Yuan Xu, Qingwen Tao
Summary: Fibroblast-activated protein-a (FAP) is overexpressed by activated fibroblasts during fibrosis or inflammation. It plays important roles in regulating the cellular responses in the synovial region of rheumatoid arthritis (RA), and its overexpression is regulated by the initial inflammatory microenvironment and epigenetic signaling. Targeted therapies for FAP are currently being developed. This review discusses the features of FAP in FLSs and its role in RA pathophysiology, as well as advances in targeted therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Mei Meng, Zhenggang Yue, Lu Chang, Yanru Liu, Jinhang Hu, Zhongxing Song, Zhishu Tang, Rui Zhou, Changli Wang
Summary: PS VII inhibits the proliferation and induces apoptosis of RA-FLS and MH7A cells by regulating the mitochondrial apoptotic pathway and the JNK and p38 MAPK pathways.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Parisa Zafari, Mahdi Taghadosi, Fatemeh Faramarzi, Misagh Rajabinejad, Alireza Rafiei
Summary: This study demonstrates that DMF treatment can suppress the proliferation and promote apoptosis of RA synovial cells, and reduce the release of inflammatory factors. These findings suggest that DMF may be considered as a therapeutic approach in the treatment of RA.
Article
Immunology
Yixiong Chen, Junlong Dang, Xiaorong Lin, Manli Wang, Yan Liu, Jingrong Chen, Ye Chen, Xiqing Luo, Zuoyu Hu, Weizhen Weng, Xiaoyi Shi, Xuan Bi, Yan Lu, Yunfeng Pan
Summary: This study found that EVs derived from RA FLSs can promote angiogenesis in ECs, primarily through the miR-1972 targeting of the p53/mTOR signaling pathway. This research provides a promising strategy for the treatment of RA patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Chuyu Shen, Yu Kuang, Shudi Xu, Ruiru Li, Jingnan Wang, Yaoyao Zou, Cuicui Wang, Siqi Xu, Liuqin Liang, Changsong Lin, Youjun Xiao, Hanshi Xu
Summary: Nitidine chloride (NC) inhibits the invasive and inflammatory actions of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) by targeting KCNH1 gene and inhibiting AKT phosphorylation, reducing the severity of arthritis in mice with RA. This discovery suggests that NC may be a novel therapeutic agent for RA, controlling FLS-mediated rheumatoid synovial inflammation and joint destruction.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mason A. McCool, Carson J. Bryant, Susan J. Baserga
BIOCHEMICAL SOCIETY TRANSACTIONS
(2020)
Article
Multidisciplinary Sciences
Carson J. Bryant, Claudia F. Lorea, Hiram Larangeira de Almeida Jr, Leticia Weinert, Leonardo Vedolin, Filippo Pinto E. Vairo, Susan J. Baserga
Summary: Alopecia, neurologic defects, and endocrinopathy (ANE) syndrome is a rare ribosomopathy caused by a variant in the RBM28 gene. A new case of ANE syndrome was reported, with the patient exhibiting alopecia, craniofacial malformations, hypoplastic pituitary, and hair and skin abnormalities. This patient had biallelic splicing variants in RBM28, resulting in skipping of mutant exons and potentially impacting protein function.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Carson J. Bryant, Mason A. McCool, Laura Abriola, Yulia Surovtseva, Susan J. Baserga
Summary: Studies of nucleolar function regulation are important for understanding the basic biology of ribosome biogenesis and developing therapeutics for cancer and ribosomopathies. Existing high-throughput assays indirectly identify drugs affecting ribosome biogenesis based on morphological changes in the nucleolus, but a more direct assay is needed. We report a high-throughput assay for nucleolar function that quantifies nucleolar rRNA biogenesis using 5-ethynyl uridine (5-EU) and nucleolar protein fibrillarin (FBL). This new method enables closer study of ribosome biogenesis in health and disease.
Article
Biochemistry & Molecular Biology
Xiongwen Cao, Alexandra Khitun, Cecelia M. Harold, Carson J. Bryant, Shu-Jian Zheng, Susan J. Baserga, Sarah A. Slavoff
Summary: This study discovered unannotated alt-proteins that play important roles in DNA damage stress and cell cycle regulation. One of these alt-proteins, MINAS-60, was found to negatively regulate assembly of the pre-60S ribosomal subunit. Depletion of MINAS-60 increases cytoplasmic 60S ribosomal subunit, leading to upregulated protein synthesis and cell proliferation.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mason A. McCool, Amber F. Buhagiar, Carson J. Bryant, Lisa M. Ogawa, Laura Abriola, Yulia V. Surovtseva, Susan J. Baserga
Summary: This study shows that the nucleolar protein RSL24D1 and the PeBoW complex play important roles in multiple steps of ribosome biogenesis, including pre-ribosomal RNA transcription and mature 28S rRNA production. They regulate pre-ribosomal RNA transcription by modulating the steady-state levels of RNA polymerase I. Specifically, RSL24D1 is demonstrated to coimmunoprecipitate with the RNA polymerase I subunit, RPA194, and together regulate the process of ribosome biogenesis.
Article
Biochemistry & Molecular Biology
Carson Bryant, Donald Atha, Vytas Reipa