Lubricin as a Therapeutic and Potential Biomarker in Sepsis

Holly Richendrfer, Gregory D Jay, Holly Richendrfer, Gregory D Jay

Abstract

Proteoglycan 4 (or lubricin), a mucin-like glycoprotein, was originally classified as a lubricating substance within diarthrodial joints. More recently, lubricin has been found in other tissues and has been implicated in 2 inflammatory pathways within the cell, via the Toll-like receptors (TLRs) and CD44. Lubricin is an antagonist of TLR2 and TLR4, and appears to enter cells via the CD44 receptor. Because of lubricin's action on these receptors, downstream processes of inflammation are halted, thereby preventing release of cytokines (a hallmark of inflammation and sepsis) from the cell, indicating lubricin's role as a biomarker and possible therapeutic for sepsis.

Keywords: CD44; Inflammasome; Inflammation; Lubricin; NF-κB; PRG4; Toll-like receptors.

Conflict of interest statement

Holly Richendrfer has no conflicts of interest

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

Figure 1:. Proposed mechanism of action of…
Figure 1:. Proposed mechanism of action of lubricin in inflammatory cascades.
Various ligands bind to both the TLRs and CD44, namely, lipopolysaccharide (LPS) and hyaluronic acid (HA). Activation of these receptors activate internal cellular pathways involved in inflammation. The inflammasome becomes activated and initiates conversion of pro IL-18 and pro-IL1β to their mature forms to be released from the cell. NF-κβ translocates to the nucleus which also initiates the production and release of other cytokines. When cells are treated with rhPRG4, these inflammatory cascades are halted. rhPRG4 strongly binds to both TLR2 and TLR4 as an antagonist and competitor with other ligands. rhRPG4 also becomes internalized into the cell via CD44 allowing rhPRG4 to both prevent activation of the inflammasome and translocation of NF-κβ thereby preventing the formation of cytokines.

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