2024年4月1日 · Only PDPN + cells mixed with platelets without the inhibitor R406 expressed phospho-Syk, which indicates that the podoplanin-CLEC-2 interaction activates Syk. We intravenously inoculated PDPN + and PDPN- cells into WT mice.

Our results support a mechanism in which PDPN on LECs binds CLEC-2 receptors on platelets and activates SYK and SLP-76 signaling to regulate blood-lymphatic vascular separation.

A monoclonal antibody to PDPN, SZ168, inhibits PDPN-induced platelet activation and aggregation in vitro and decreases the incidence of VTE in mice. High PDPN expression of the pulmonary squamous cell carcinoma is associated with an increased risk of VTE and poor prognosis of the patients.

2022年12月26日 · Podoplanin (PDPN) is intensely expressed on the podocyte membrane in an evolutionally conserved manner. CLEC-2, the endogenous ligand of PDPN, is highly expressed in platelets and also exists in...

Pdpn-/-mice develop normally until around day E10, which coincides with the appearance of PDPN protein. From days E10–16, approximately 40% of Pdpn-/-embryos die; the ones that survive to birth die within a few days (Mahtab et al., 2008).

PDPN on LECs or FRCs activates CLEC-2 in platelets, triggering platelet activation and/or aggregation through downstream signaling events, including activation of Syk kinase. This mechanism is required to initiate and maintain separation of blood and lymphatic vessels and to stabilize high endothelial venule integrity within lymphnodes.

Src/Syk-dependent signalling stabilises platelet adhesion to podoplanin, providing a possible molecular mechanism contributing to the lymphatic defects of Syk-deficient mice. Keywords: Platelet physiology; adhesion molecules; lymphatics; rheology; signal transduction.

PDPN is expressed by lymphatic endothelial and fibroblastic reticular cells and promotes blood-lymph separation during development by activating the C-type lectin receptor, CLEC-2, on platelets. Here, we describe a role for CLEC-2 in the morphodynamic behavior and …

The syk-dependent signalling pathway plays a role in platelet aggregation and melanoma metastasis. PDPN binding to CLEC-2 induces Syk-dependent signalling in platelets. We used the Syk inhibitor R406 to block platelet binding to tumour cells to assess the role of Syk in the PDPN-CLEC-2 interaction.

2024年11月11日 · We show that CLEC5A is a cell surface receptor activated by podoplanin (PDPN) and induces TAM polarization through Syk-JAK-STAT3 signaling.