Dysfunctional O-glycosylation exacerbates LPS-induced ARDS in mice through impairment of podoplanin expression on alveolar macrophages

Podoplanin and CLEC-2 levels in patients with COVID-19

“…More recently, the anti-inflammatory effects of this pathway in sepsis models were explained by the release of complement inhibitors by monocytes induced by podoplanin [ 41 ]. A protective effect of the podoplanin/CLEC-2 pathway was also demonstrated in a model of acute lung injury based on the intratracheal instillation of lipopolysaccharide, in which lung injury was significantly higher in mice with CLEC-2 or podoplanin deficiency [ 26 , 27 ]. Together, these data raise the hypothesis that podoplanin could be involved in both the inflammatory and prothrombotic state observed in patients with COVID-19.…”

“…More recently, podoplanin has been involved in the pathogenesis of thrombosis, not only in animal models [ 19 , [22] , [23] , [24] ] but also in clinical studies that showed that expression of PDPN in brain tumors is an independent predictor of thrombotic risk [ 25 ]. Interestingly, emerging evidence also demonstrated that podoplanin is involved in other compartments of innate immune response, as suggested by its protective effect in animal models of acute lung injury and sepsis [ 26 , 27 ]. Interestingly, both podoplanin and angiotensin-converting enzyme 2 (ACE2), which is the main receptor by which SARS-CoV-2 invades lung epithelial cells [ 28 ], are expressed in lungs by alveolar type 1 cells [ [29] , [30] , [31] ].…”

Analysis of N‐ and O‐linked site‐specific glycosylation by ion mobility mass spectrometry: State of the art and future directions

“…Glycosylation is a form of PTM that impacts a multitude of cellular events such as intercellular communication and ligand-receptor recognition [11][12][13][14][15][16]. Protein glycosylation has various subclasses, but the most widely examined subclasses are (1) N-glycosylation, which occurs on an asparagine (Asn) residue in the sequence motif Asn-X-Ser/Thr (X = any amino acid except proline); and (2) O-glycosylation, which occurs on a Ser or Thr residue [17][18][19]. For example, two proteins may have the same glycans attached, but the stereochemistry of these glycans can be different, resulting in distinct proteoforms [20].…”