Breaking down chronic inflammatory diseases: the role of biglycan in promoting a switch between inflammation and autophagy. (27th February 2019)

• Record Type: Journal Article
• Authors: Roedig, Heiko; Nastase, Madalina Viviana; Wygrecka, Malgorzata; Schaefer, Liliana
• Is Part Of: FEBS journal. Volume 286:Number 15(2019)
• Page Start: 2965
• Page End: 2979
• Publication Date: 2019-02-27
• Subjects: CD14 -- CD44 -- DAMP -- diabetes mellitus -- extracellular matrix -- lupus nephritis -- macrophage -- T helper cells -- toll‐like receptor; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14791
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : It is well established that biglycan, a small leucine‐rich proteoglycan, acts as an extracellular matrix‐derived danger signal in its soluble form. By binding to innate immunity Toll‐like receptors (TLR) 2 and 4, biglycan initiates and perpetuates the inflammatory response. Previous work has conveyed that biglycan's role in inflammation extends far beyond its function as a canonical danger signal. It has been shown that biglycan acts in an anti‐inflammatory capacity, wherein it tightly regulates the inflammatory response. In this review, we will discuss a paradigm shift to our understanding of biglycan signaling in inflammation. Mounting evidence suggests that the selective interactions between biglycan, TLRs, and their adapter proteins critically regulate downstream signaling and disease outcome. Biglycan can act as a high‐affinity ligand for TLR coreceptors CD14 and CD44, further providing an additional layer of complexity. We propose a novel concept, that biglycan steers signaling toward inflammation by interacting with CD14, whereas it can trigger autophagy by binding to CD44. Thus, biglycan, and perhaps others soluble proteoglycans, could function as molecular switches which could either propagate the signaling of chronic inflammation or promote the resolution of inflammatory processes. Obviously, these new functions have broad implications in the regulation of various inflammatory diseases and could provide the basis for developing novel therapeutic regimens that would selectively target the interactions between biglycan, TLRs, coreceptors, and adapter molecules. Abstract : Biglycan, a small leucine‐rich proteoglycan, acts as an extracellular matrix‐derived danger signal in its soluble form. Via selective interaction with Toll‐like receptors (TLR), their coreceptors and adaptors, biglycan critically regulates downstream signaling and disease outcome. Here, we emphasize the role of CD14 and CD44 in the biglycan‐mediated TLR signaling in triggering either inflammation or autophagy with implications in inflammatory diseases.