Elevated levels of soluble Endothelial protein C receptor in rheumatoid arthritis and block the therapeutic effect of protein C in collagen-induced arthritis

Bai, Li; Liu, Wenjia; Guo, Pengnian; Bai, Jingru; Liu, Yuan; Hua, Yana; Pang, Chunyan; Zhang, Wei; Yin, Fangrui; Wang, Yongfu

doi:10.1016/j.intimp.2020.106255

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…EPCR participates in PC pathway, which relates to anticoagulant, anti-inflammation and vascular barrier protection, and has been proved to prevent thrombosis in vivo directly (Centelles et al 2010). EPCR can be shed from the cell surface into plasma as a soluble form, the improvement of sEPCR level was discovered in some infectious diseases and autoimmune diseases (Bai et al 2020;Zhu et al 2015;Chiappetta et al 2016). In recent years, much attention has been appealed to the roles of EPCR in differential pathophysiology like the cancer and malaria, because of the ligands diversity (Pendurthi and Rao.…”

Section: Discussionmentioning

confidence: 99%

Andrographolide Inhibits PMA-Induced EPCR Shedding through JNK and p38 MAPK

Wang

Liang

et al. 2022

Preprint

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Endothelial cell protein C (EPCR), one of the main members in the protein C (PC) pathway, plays an important role in the process of coagulation and inflammation. EPCR can shed from the cell membrane, which process is mediated by the tumor necrosis factor-α converting enzyme (TACE) and related to some diseases. Andrographolide is the major constituent of Andrographis paniculata, a kind of herbal medicine commonly used in clinical for its various pharmacological actions, especially anti-inflammation and anti-cancer. In this study, we investigated andrographolide protection for EPCR and its potential molecular mechanism. Phorbol-12-myristate-13-acetate (PMA)-stimulated human umbilical vein endothelial cells (HUVECs) were used to be the model of EPCR shedding and the andrographolide pretreatment was tested in this model. The results showed that andrographolide could reduce PMA-induced EPCR shedding and inhibit the TACE function. Additionally, we found andrographolide also suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38, but had no effect on extracellular regulated protein kinase (ERK) 1/2. Given these results, andrographolide can inhibit the shedding of EPCR by the suppression of TACE, which may take JNK and p38 as the molecular target. These findings indicated a substantial anti-EPCR shedding efficacy of andrographolide in vitro.

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Section: Discussionmentioning

confidence: 99%

Andrographolide Inhibits PMA-Induced EPCR Shedding through JNK and p38 MAPK

Wang

Liang

et al. 2022

Preprint

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“…(sEPCR) forms, the former being expressed by CD4 + T cells. Lower levels of CD4 + EPCR + Tcells and higher levels of sEPCR have been observed in RA compared to osteoarthritis and sEPCR showed a positive correlation with clinical and laboratory parameters of RA (63). In-vitro experiments demonstrated that sEPCR inhibited Th17 activation, modifying the Th17/Treg balance alleviating disease progression.…”

Section: Adaptive Immune Responsementioning

confidence: 92%

One year in review 2021: pathogenesis of rheumatoid arthritis

Picerno

Ferro

Adinolfi

et al. 2021

Clinical and Experimental Rheumatology

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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by local and systemic inflammation where the close interaction between immune cells and soluble mediators leads to amplification and perpetuation of inflammatory and remodelling processes. The research carried out in the last year in the field of RA has made it possible to identify new mechanisms involved in the pathogenesis of the disease, enabling the discovery of new potential therapeutic targets. Thus, in this review we summarise new insights in RA pathogenesis, resulting from a literature research date published in the last year.

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“…This ligand competes with APC for the same ligand binding site [129], which interferes with regular APC-EPCR interactions and stimulates RA synovial proliferation and destruction [109]. This may also contribute to the production of sEPCR since the sera of arthritic mice have significantly higher levels of sEPCR than healthy controls [109,146]. Short-cut mRNA is increased in RA patients compared to osteoarthritis patients, indicating that variable EPCR mRNA splicing plays a key role in the overproduction of sEPCR in RA patients [146].…”

Section: Epcr and Ramentioning

confidence: 99%

“…This may also contribute to the production of sEPCR since the sera of arthritic mice have significantly higher levels of sEPCR than healthy controls [109,146]. Short-cut mRNA is increased in RA patients compared to osteoarthritis patients, indicating that variable EPCR mRNA splicing plays a key role in the overproduction of sEPCR in RA patients [146].…”

Section: Epcr and Ramentioning

confidence: 99%

Endothelial Protein C Receptor and Its Impact on Rheumatic Disease

O’Hehir,

Lynch,

O’Neill

et al. 2024

JCM

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Endothelial Protein C Receptor (EPCR) is a key regulator of the activated protein C anti-coagulation pathway due to its role in the binding and activation of this protein. EPCR also binds to other ligands such as Factor VII and X, γδ T-cells, plasmodium falciparum erythrocyte membrane protein 1, and Secretory group V Phospholipases A2, facilitating ligand-specific functions. The functions of EPCR can also be regulated by soluble (s)EPCR that competes for the binding sites of membrane-bound (m)EPCR. sEPCR is created when mEPCR is shed from the cell surface. The propensity of shedding alters depending on the genetic haplotype of the EPCR gene that an individual may possess. EPCR plays an active role in normal homeostasis, anti-coagulation pathways, inflammation, and cell stemness. Due to these properties, EPCR is considered a potential effector/mediator of inflammatory diseases. Rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are autoimmune/inflammatory conditions that are associated with elevated EPCR levels and disease activity, potentially driven by EPCR. This review highlights the functions of EPCR and its contribution to rheumatic diseases.

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Elevated levels of soluble Endothelial protein C receptor in rheumatoid arthritis and block the therapeutic effect of protein C in collagen-induced arthritis

Cited by 7 publications

References 39 publications

Andrographolide Inhibits PMA-Induced EPCR Shedding through JNK and p38 MAPK

Andrographolide Inhibits PMA-Induced EPCR Shedding through JNK and p38 MAPK

One year in review 2021: pathogenesis of rheumatoid arthritis

Endothelial Protein C Receptor and Its Impact on Rheumatic Disease

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