2009), indicating that biglycan may act as a danger associated molecular pattern (DAMP) that is proteolytically released from the ECM upon tissue stress or injury and then turn on host innate and adaptive immune responses (Kalamajski and Oldberg 2009 Schaefer et al. Biglycan was also reported involved in the activation of NLRP3 inflammasome via the cooperativity of TLR2/TLR4 and P2X receptors leading to the secretion of mature IL-1 β both in a model of non-infectious inflammatory renal injury and in LPS induced sepsis (Babelova et al. 2005), indicating a self-amplifying loop involving biglycan exists in the pathway leading to macrophage activation. In addition, biglycan itself can activate macrophages and activated macrophages will synthesize and secrete biglycan (Schaefer and Iozzo 2008 Schaefer et al. As endogenous ligands for TLR 4 and TLR 2, decorin and biglycan stimulate macrophages to produce TNF α, IL-12, and MIP 2 (Schaefer et al.
The best studied signaling pathway in innate immune responses activated by SLRPs is mediated by TLR4/2. Indeed, certain SLRPs such as biglycan were described as “analogous to PAMPs” in some studies due to their ability to induce innate immune response by their own without the need of PAMPs (Schaefer et al. The leucine-rich repeat motifs in the core protein of SLRPs and the structural similarity between SLRPs and the pathogen associated molecular patterns (PAMPs) suggest that SLRPs play a role in host immunity (Shao et al. Because host immune responses play an important part in the pathogenesis of renal diseases, the role of SLRPs in this set of diseases will also be discussed. Current review will specifically focus on the role of SLRPs in host immune responses. With more and more studies focused on this family in recent years, the category of the physiological functions and pathological roles of SLPRs are involving rapidly. Recent studies also demonstrate that SLRP family members are involved in different signaling pathways including TGF-β/Nodal/Smad2 pathway, BMP/Smad1 pathway, EGF pathway, MAPK/FGF pathway, TLR pathway, purinergic pathway and mTOR signaling pathway, indicating an essential role of this family in coordinating other important cellular processes such as fibrosis, autophagy and host immune responses etc (Dellett et al. 2012 Schaefer and Iozzo 2008 Kalamajski and Oldberg 2009 Keene et al. Besides being an important component of ECM, SLRPs have been implicated in cell proliferation and migration (Dellett et al. So far, biglycan and decorin from class I are among the best studied SLRPs in a variety of biological and pathological processes (Dellett et al. The unique structural characteristics of GAG types provide some of the structural basis for the multitude of the biological functions of SLRPs (Theocharis et al. The SLRP family currently has 17 members that are grouped into five distinct classes based on their conservation and homology at the protein and genomic levels, the number of the LRRs, the spacing of the N-terminal cysteine residues in the protein cores, and their chromosomal organization (Fig.
The small leucine rich proteoglycans (SLRPs), named after their relatively small size and the leucine rich repeats (LRR) in their structures, consist of two main structural components: protein cores and various glycosaminoglycan (GAG) side chains, which form decorin, biglycan, and lumican etc (Dellett et al.
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