Phosphatidylserine externalized on the colonic capillaries as a novel pharmacological target for IBD therapy

Zhang, Xuerui; Song, Lulu; Li, Lin; Zhu, Banghui; Huo, Liqun; Hu, Zhang; Wang, Xinran; Wang, Jie; Gao, Mengyue; Zhang, Jing; Zhang, Hua

doi:10.1038/s41392-021-00626-z

Cited by 11 publications

(5 citation statements)

References 52 publications

(47 reference statements)

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“…Thus, Annexin V(A5) (ANXA5) is a calcium-dependent protein that binds to anionic phospholipids (PS, CL, etc.). ANXA5 has been shown to effectively ameliorate TNBS-induced colitis by inhibiting inflammatory cell infiltration [ 234 ].…”

Section: Major Iecs’ Phospholipids Their Metabolism the Role In Ibd And Therapeutic Potentialmentioning

confidence: 99%

Fat of the Gut: Epithelial Phospholipids in Inflammatory Bowel Diseases

Boldyreva

Морозова

Saydakova³

et al. 2021

IJMS

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Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic inflammation within the gastrointestinal (GI) tract. Despite the significant progress in understanding the etiology and development of treatment strategies, IBD remain incurable for thousands of patients. Metabolic deregulation is indicative of IBD, including substantial shifts in lipid metabolism. Recent data showed that changes in some phospholipids are very common in IBD patients. For instance, phosphatidylcholine (PC)/phosphatidylethanolamine (PE) and lysophosphatidylcholine (LPC)/PC ratios are associated with the severity of the inflammatory process. Composition of phospholipids also changes upon IBD towards an increase in arachidonic acid and a decrease in linoleic and a-linolenic acid levels. Moreover, an increase in certain phospholipid metabolites, such as lysophosphatidylcholine, sphingosine-1-phosphate and ceramide, can result in enhanced intestinal inflammation, malignancy, apoptosis or necroptosis. Because some phospholipids are associated with pathogenesis of IBD, they may provide a basis for new strategies to treat IBD. Current attempts are aimed at controlling phospholipid and fatty acid levels through the diet or via pharmacological manipulation of lipid metabolism.

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Section: Major Iecs’ Phospholipids Their Metabolism the Role In Ibd And Therapeutic Potentialmentioning

confidence: 99%

Fat of the Gut: Epithelial Phospholipids in Inflammatory Bowel Diseases

Boldyreva

Морозова

Saydakova³

et al. 2021

IJMS

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“…HUVECs have the potential of stem cells and are frequently selected as cell models for endothelial cell experiments, including IBD experiments. [ 31 ] The bioactive peptides in bovine whey, oyster soft tissue, and sturgeon muscle were all demonstrated to have the anti‐inflammatory effect on suppressing the expression of the inflammatory cytokines in RAW264.7 macrophages cells. Thus, the RAW264.7 macrophages were generally used as a cell model to evaluate the anti‐inflammatory effect of bioactive compounds as its sensitivity to immune stimulation.…”

Section: Resultsmentioning

confidence: 99%

Surface‐Engineered Vanadium Carbide MXenzyme for Anti‐Inflammation and Photoenhanced Antitumor Therapy of Colon Diseases

Deng

Xian

Cai

et al. 2023

Adv Funct Materials

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The development of colitis-associated colorectal cancer is known to be associated with the inflammation-dysplasia-carcinoma pathway, and thus, chronic inflammation represents an inducer and promoter of cancer. To inhibit the evolution from colitis to colorectal cancer and provide an efficient anticancer therapy, a surface-engineered vanadium carbide MXene nanoenzyme (MXenzyme) is developed with both amino functionalization and gallium doping (Ga/V 2 C-NH 2 ). Benefiting from multiple enzymemimicking activities, MXenzymes have shown great potential to decrease excessive reactive oxygen species and inhibit the levels of proinflammatory cytokines, resulting in good anti-inflammatory effects on dextran sulfate sodium-induced acute colitis. Moreover, the gallium-doped MXene with an amino-functionalized surface can mediate improved MXene-tumor interactions and inhibitory effects on cell proliferation, achieving precise and efficient chemo-photothermal therapy. Elemental doping into MXene is also highlighted as a feasible strategy to achieve the loading and controlled release of gallium. As a result, complete tumor ablation without further recurrence is observed for the colon cancer-bearing mice that receive Ga/V 2 C-NH 2 and near infrared irradiation, while the MXenzyme system displays excellent biocompatibility at both the cellular and animal levels. These findings not only enrich the research of MXene, but also illustrate its efficient therapeutic promise in anti-inflammation and photoenhanced antitumor therapy of colon diseases.

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“…Furthermore, PS externalized by antigen-stimulated CD8 T cells is linked to T cell activation, with increased expression of CD69 and levels of IFN-γ, IL-2, and TNF-α reported 42 . In trinitrobenzene sulfonic acid (TNBS)-induced colitis, PS inhibition by annexin A5 alleviated disease via reduced inflammatory cell infiltration due to inhibition of endothelial cell activation 43 . Furthermore, pups reared on artificial milk with the addition of lactadherin, the PS binding and blocking glycoprotein, displayed increased levels of tolerogenic CD3 + CD4 + CD25 + T cells in their Payer's patches compared to pups reared on artificial milk alone 44 .…”

Section: Discussionmentioning

confidence: 99%

Tissue factor-dependent colitogenic CD4+ T cell thrombogenicity is regulated by activated protein C signalling

Leon,

Klavina,

Rehill

et al. 2024

Preprint

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Inflammatory bowel disease (IBD) patients experience up to 6-fold increased risk of venous thromboembolism (VTE) compared to the general population, although the mechanistic basis for this increased risk remains poorly defined. We found that colitogenic CD4+ T cells express tissue factor (TF) and promote rapid TF-dependent plasma thrombin generation in T cell-dependent calibrated automated thrombinography assays. Furthermore, we identified the presence of TF+CD4+CD3+ T cells in the colons of both mice with colitis and paediatric IBD patients during active disease. TF is typically expressed in an 'encrypted' state and requires decryption for optimal procoagulant activity. Notably, flow cytometric analysis demonstrated that activated CD4+ T cells express significantly increased acid sphingomyelinase and protein disulphide isomerase, critical mediators for TF decryption, on their cell membrane compared to naive T cells. The protein C (PC) pathway is an important regulator of TF-mediated thrombin generation. Pertinently, pre-clinical studies suggest an important role for diminished PC pathway activity in IBD pathophysiology. To understand how this process might be regulated, we performed meta-transcriptomic and gene expression analysis of IBD patient gut biopsy tissue, identifying dysregulated expression of genes involved in the regulation of coagulation, including PC (PROC) and its receptor (EPCR; PROCR). Subsequent functional studies revealed that activated protein C (APC) signalling reduced colitogenic T cell generation and activity, potently impaired TF decryption and significantly reduced T cell-mediated thrombin generation and clot formation. These data identify TF-mediated colitogenic T cell thrombogenicity and demonstrate a new role for APC signalling in regulating T cell thrombo-inflammatory activity.

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Phosphatidylserine externalized on the colonic capillaries as a novel pharmacological target for IBD therapy

Cited by 11 publications

References 52 publications

Fat of the Gut: Epithelial Phospholipids in Inflammatory Bowel Diseases

Fat of the Gut: Epithelial Phospholipids in Inflammatory Bowel Diseases

Surface‐Engineered Vanadium Carbide MXenzyme for Anti‐Inflammation and Photoenhanced Antitumor Therapy of Colon Diseases

Tissue factor-dependent colitogenic CD4+ T cell thrombogenicity is regulated by activated protein C signalling

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