Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.1.53 (
sialidase
)
2,694
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
O-glycosylation of
podoplanin
(
PDPN
) on lymphatic endothelial cells is critical for the separation of blood and lymphatic systems by interacting with platelet C-type lectin-like receptor 2 during development. However, how O-glycosylation controls endothelial
PDPN
function and expression remains unclear. In this study, we report that core 1 O-glycan-deficient or desialylated
PDPN
was highly susceptible to proteolytic degradation by various proteases, including metalloproteinases (MMP)-2/9. We found that the lymph contained activated MMP-2/9 and incubation of the lymph reduced surface levels of
PDPN
on core 1 O-glycan-deficient endothelial cells, but not on wild-type ECs. The lymph from mice with sepsis induced by cecal ligation and puncture, which contained bacteria-derived
sialidase
, reduced
PDPN
levels on wild-type ECs. The MMP inhibitor, GM6001, rescued these reductions. Additionally, GM6001 treatment rescued the reduction of
PDPN
level on lymphatic endothelial cells in mice lacking endothelial core 1 O-glycan or cecal ligation and puncture-treated mice. Furthermore, core 1 O-glycan-deficient or desialylated
PDPN
impaired platelet interaction under physiological flow. These data indicate that sialylated O-glycans of
PDPN
are essential for platelet adhesion and prevent
PDPN
from proteolytic degradation primarily mediated by MMPs in the lymph.
...
PMID:Podoplanin requires sialylated O-glycans for stable expression on lymphatic endothelial cells and for interaction with platelets. 2533 27
