Common Denominators of Extracellular Matrix across Tissues as Inter-Tissue Messengers and Targets for Drug Repurposing

Dear Colleagues,

Cells secrete diverse proteoglycans, glycans, and glycoproteins, which aggregate in the extracellular space and form extracellular matrix (ECM) structures. The ECM shapes cell differentiation and migration during early development, and provides mechanical support to cells and tissues. It serves as a diffusion barrier, extracellular scaffold for compartmentalization, and signaling platform for intercellular communications, and regulates diverse cellular functions in tissue homeostasis.

The molecular composition and organization of ECM in different tissues vary according to the tissue functions, so the ECM in cartilage is optimal for viscoelasticity and lubrication, while in bones it is a durable, strong, and stiff structure with low elasticity for shock absorption. Still, the molecular diversity of major ECM components is limited, and several forms of ECM can be distinguished in diverse tissues, with a remarkable similarity of organizational principles of basal lamina-like structures in the neuromuscular junctions and vasculature or hyaluronic acid-lectican-based scaffolds in the cartilage and the brain.

In this Special Issue, we aim to explore this similarity in the molecular organization as a potential basis for an exchange of ECM-targeting tools and therapeutics for diseases affecting the ECM in different organs, including the brain, cartilage, kidney, and vascular system. Differences between ECM in different tissues and ECM degradation products generated during disease are also of relevance, for instance, to understand how ECM structures can be targeted in a tissue-specific manner and which ECM molecules can be used as diagnostic biomarkers. Particularly (but not exclusively) we expect to collect reviews as well as experimental and bioinformatic studies with a focus on:

• Cross-tissue comparison of signaling mechanisms impaired in human carriers of ECM mutations or corresponding animal models;
• Bioinformatic analysis of common dysregulations in ECM molecules and related proteases and glycans across diseases;
• Cross-signaling in and between organs via ECM molecules and their proteolytic products;
• Immunomodulatory effects of ECM and its proteolytic products;
• Drugs targeting biosynthesis, glycosylation, proteolysis, and other posttranslational modifications of ECM molecules and their receptors.

We anticipate that this Issue will promote interactions between experts working on ECM in different organs and tissues and will facilitate the transfer of targeting strategies across fields. As an example, beneficial effects by neural ECM modifications are envisioned given their multiple functional roles and relevance for neurological and psychiatric diseases; however, ECM-targeting therapeutics are still to be developed. For other organs, similar approaches are also foreseen, for example, to counteract aging and inflammatory diseases.

Prof. Dr. Alexander Dityatev
Prof. Dr. Jessica Bertrand
Prof. Dr. Peter R. Mertens
Guest Editors

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• proteoglycans
• glycans
• glycoproteins
• matricellular proteins
• integrins
• matrix metalloproteinases
• extracellular scaffold
• cell signaling
• ECM remodeling