The Role of CLEC-2 and Its Ligands in Thromboinflammation

Meng, Danyang; Luo, Man; Liu, Beibei

doi:10.3389/fimmu.2021.688643

Cited by 38 publications

(34 citation statements)

References 99 publications

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“…CLEC1b (CLEC-2) is a C-type lectin-like receptor 2 that is expressed on B lymphocytes, granulocytes, monocytes, and dendritic cells, as well as Kupffer cells and platelets, and binds to various ligands including the mucin-like protein podoplanin (PDPN) [ 53 ]. It was found that LPS and other inducers of inflammation can increase the expression of CLEC-2, but this is not typical for all macrophage subpopulations [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

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MARCO+ Macrophage Dynamics in Regenerating Liver after 70% Liver Resection in Mice

et al. 2021

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Background: Macrophages play a key role in liver regeneration. The fates of resident macrophages after 70% resection are poorly investigated. In this work, using the MARCO macrophage marker (abbreviated from macrophage receptor with collagenous structure), we studied the dynamics of mouse liver resident macrophages after 70% resection. Methods: In BALB/c male mice, a model of liver regeneration after 70% resection was reproduced. The dynamics of markers CD68, TIM4, and MARCO were studied immunohistochemically and by using a Western blot. Results: The number of MARCO- and CD68-positive macrophages in the regenerating liver increased 1 day and 3 days after resection, respectively. At the same time, the content of the MARCO protein increased in the sorted macrophages of the regenerating liver on the third day. Conclusions: The data indicate that the number of MARCO-positive macrophages in the regenerating liver increases due to the activation of MARCO synthesis in the liver macrophages. The increased expression of MARCO by macrophages can be regarded as a sign of their activation. In the present study, stimulation with LPS led to an increase in the expression of the Marco gene in both Kupffer cells and macrophages of bone marrow origin.

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Section: Discussionmentioning

confidence: 99%

“…It was found that LPS and other inducers of inflammation can increase the expression of CLEC-2, but this is not typical for all macrophage subpopulations [ 54 ]. According to some data, CLEC-2 in Kupffer cells is detected at a low level [ 53 ], while it can participate in the secretion of proinflammatory cytokines [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

MARCO+ Macrophage Dynamics in Regenerating Liver after 70% Liver Resection in Mice

et al. 2021

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“…C-type lectin-like receptor 2 (CLEC-2), which is a platelet receptor, binds to PDPN and plays a critical role in PDPN-mediated platelet aggregation and lung metastases [15][16][17]. CLEC-2 was first discovered as a platelet receptor for snake venom, rhodocytin, known as a platelet aggregation-inducing toxin [18][19][20].…”

Section: Molecular Functions Of Pdpn Extracellular Domainmentioning

confidence: 99%

Roles of Podoplanin in Malignant Progression of Tumor

Suzuki

Kaneko

Kato

2022

Cells

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Podoplanin (PDPN) is a cell-surface mucin-like glycoprotein that plays a critical role in tumor development and normal development of the lung, kidney, and lymphatic vascular systems. PDPN is overexpressed in several tumors and is involved in their malignancy. PDPN induces platelet aggregation through binding to platelet receptor C-type lectin-like receptor 2. Furthermore, PDPN modulates signal transductions that regulate cell proliferation, differentiation, migration, invasion, epithelial-to-mesenchymal transition, and stemness, all of which are crucial for the malignant progression of tumor. In the tumor microenvironment (TME), PDPN expression is upregulated in the tumor stroma, including cancer-associated fibroblasts (CAFs) and immune cells. CAFs play significant roles in the extracellular matrix remodeling and the development of immunosuppressive TME. Additionally, PDPN functions as a co-inhibitory molecule on T cells, indicating its involvement with immune evasion. In this review, we describe the mechanistic basis and diverse roles of PDPN in the malignant progression of tumors and discuss the possibility of the clinical application of PDPN-targeted cancer therapy, including cancer-specific monoclonal antibodies, and chimeric antigen receptor T technologies.

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“…CLEC-2 and its ligands serve as a molecular link between platelets, immune cells, and target cells, as well as a unique mechanism for thrombosis. As a result, CLEC-2-related pathways could be used to treat thromboinflammation [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Researchers discovered that podoplanin was upregulated in the venous wall while trying to figure out the mechanism of cancer-mediated inflammation. CLEC-2 may thus have a role in tumour-induced thromboinflammation, and persistent long-term exposure to inflammatory cytokines causes thrombosis [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin-Based Inhibitors of Thrombosis and Cancer Metastasis Promoting Factor CLEC 2 from Traditional Medicinal Species Curcuma longa

Manivannan

Carmena-Bargueño

Devaraju³

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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The CLEC-2 receptor protein belongs to the C-type lectin superfamily of transmembrane receptors that have one or more C-type lectin-like domains. CLEC-2 is a physiological binding receptor of podoplanin (PDPN), which is expressed on specific tumour cell types and involved in tumour cell-induced platelet aggregation and tumour metastasis. CLEC-2 and podoplanin-expressing tumour cells interact to increase angiogenesis, tumour development, and metastasis. CLEC-2 is a hemi-immunoreceptor tyrosine-based activation motif (hemi-ITAM) receptor located on platelets and a subset of dendritic cells that are expressed constitutively. This molecule is secreted by activated platelets around tumours and has been shown to inhibit platelet aggregation and tumour metastasis in colon carcinoma by binding to the surface of tumour cells. Pharmacokinetic studies were carried using a DrugLiTo, and molecular docking was performed using AutoDock Tools 1.5.6 (ADT). Twenty-nine bioactive compounds were included in the study, and four of them, namely, piperine, dihydrocurcumin, bisdemethoxycurcumin, and demothoxycurcumin, showed potential antagonist properties against the target. The resultant best bioactive was compared with commercially available standard drugs. Further, validation of respective compounds with an intensive molecular dynamics simulation was performed using Schrödinger software. To the best of our knowledge, this is the first report on major bioactive found on clove as natural antagonists for CLEC-2 computationally. To further validate the bioactive and delimit the screening process of potential drugs against CLEC-2, in vitro and in vivo studies are needed to prove their efficacy.

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The Role of CLEC-2 and Its Ligands in Thromboinflammation

Cited by 38 publications

References 99 publications

MARCO+ Macrophage Dynamics in Regenerating Liver after 70% Liver Resection in Mice

MARCO+ Macrophage Dynamics in Regenerating Liver after 70% Liver Resection in Mice

Roles of Podoplanin in Malignant Progression of Tumor

Curcumin-Based Inhibitors of Thrombosis and Cancer Metastasis Promoting Factor CLEC 2 from Traditional Medicinal Species Curcuma longa

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