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Review
. 2023 Jul:29:521-536.
doi: 10.1016/j.jtos.2023.06.013. Epub 2023 Jun 22.

Small leucine rich proteoglycans: Biology, function and their therapeutic potential in the ocular surface

Affiliations
Review

Small leucine rich proteoglycans: Biology, function and their therapeutic potential in the ocular surface

Tarsis Ferreira Gesteira et al. Ocul Surf. 2023 Jul.

Abstract

Small leucine rich proteoglycans (SLRPs) are the largest family of proteoglycans, with 18 members that are subdivided into five classes. SLRPs are small in size and can be present in tissues as glycosylated and non-glycosylated proteins, and the most studied SLRPs include decorin, biglycan, lumican, keratocan and fibromodulin. SLRPs specifically bind to collagen fibrils, regulating collagen fibrillogenesis and the biomechanical properties of tissues, and are expressed at particularly high levels in fibrous tissues, such as the cornea. However, SLRPs are also very active components of the ECM, interacting with numerous growth factors, cytokines and cell surface receptors. Therefore, SLRPs regulate major cellular processes and have a central role in major fundamental biological processes, such as maintaining corneal homeostasis and transparency and regulating corneal wound healing. Over the years, mutations and/or altered expression of SLRPs have been associated with various corneal diseases, such as congenital stromal corneal dystrophy and cornea plana. Recently, there has been great interest in harnessing the various functions of SLRPs for therapeutic purposes. In this comprehensive review, we describe the structural features and the related functions of SLRPs, and how these affect the therapeutic potential of SLRPs, with special emphasis on the use of SLRPs for treating ocular surface pathologies.

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Conflict of interest statement

Declaration of competing interest Authors have no conflicts or financial interests related to this manuscript to disclose.

Figures

Fig. 1.
Fig. 1.
SLRPs motif conservation and distribution through phylogeny. (A) Dendrogram of five distinct families of SLRPs and related LRR proteins. (B) Distribution of conserved motifs and family specific motifs, as calculated by the multiple Em for motif Elicitation (MEME) suite [306]. (C) Sequence descriptor of graphical topology from B.
Fig. 2.
Fig. 2.
General structure of SLRPs. (A) SLRPs overall arched structure (white), with beta sheet on its concave side (blue) that participate in most of SLRP-ligand interactions. Some SLRPs show a N-terminal cysteine cluster (yellow) provides the structural stability for the protein to fold, and some also have a C-terminal cysteine cluster stabilize the folded protein. Additionally, some SLRPs have an “ear repeat” (purple) with unknown function. Other characteristics not displayed include proline, arginine and lysine amino acid clusters and tyrosine sulfation. Finally, chains can be N- or O-glycosylated. (B) Detail of a leucine rich repeat, convex shape defines curvature by the presence of alpha-helices (more curved) or turns (less curved). Fold is maintained by leucines at the hydrophobic core (white sticks) and binding is promoted by residues at the concave face (blue sticks).
Fig. 3.
Fig. 3.
Circular plot of the various identified functions of decorin, biglycan, lumican, and fibromodulin. Green indicates stimulates or promotes; blue indicates inhibits or prevents and purple indicates a dual function, where, depending on the physiological condition it can sometimes stimulate/promote and sometimes inhibit/prevent.

References

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