Breaking down chronic inflammatory diseases: the role of biglycan in promoting a switch between inflammation and autophagy

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.

Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease

“…Adipose tissue makes large quantities of ECM during active remodeling, as would occur during WAT expansion in obesity (390)(391)(392). Obese animal models and humans with obesity and/or T2DM exhibit large increases in visceral WAT ECM content, which can contribute to the local inflammatory milieu (393,394). To date, most studies of WAT ECM function have centered around collagen, which can form a scaffold that constrains adipocyte expansion due to mechanical stress (391,392,395).…”

Integral Roles of Specific Proteoglycans in Hair Growth and Hair Loss: Mechanisms behind the Bioactivity of Proteoglycan Replacement Therapy with Nourkrin® with Marilex® in Pattern Hair Loss and Telogen Effluvium

“…More recent studies have brought some of the anti-inflammatory activities of biglycan into light, including its role in regulating the balance of IL-1β synthesis [60]. e sum of evidence suggests that biglycan is a switcher between inflammation and autophagy, which determines the chronicity or resolution of an inflammatory response (discussed in detail by Roedig et al) [61]. is dual pro-and anti-inflammatory character has also been observed in decorin.…”

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“…Biglycan has the function of reducing the growth rate and bone mass of mice [ 115 ]. Recently research also found that biglycan may be a molecular switch between inflammation and autophagy [ 116 ].…”

“…This process is realized by CD44/TLR4 signaling axis. Subsequently, Roedig et al [ 116 ] discussed the mechanism of BGN as a molecular switch, triggering signals in both directions of promoting inflammation and autophagy. Therefore, it is necessary to selectively develop novel therapeutic regimens targeting the interactions between biglycan, TLRs, coreceptors, and adapter molecules.…”