Glucocorticoid-Mediated Extracellular Matrix Regulation: Implications for Precision Therapy

Figures

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  Figure 1. An overview of the studies collection for this study.

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  Figure 2. Schematic illustration of the state of the extracellular matrix (ECM) under pathological conditions. The central part is the normal ECM. (A) Taking osteoarthritis as an example, the diagram shows a comparison of healthy cartilage ECM with osteoarthritic cartilage ECM. In osteoarthritic cartilage ECM, elevated MMPs and inflammatory factors degrade collagen and proteoglycans. Chondrocytes, influenced by these degradation products and inflammatory factors, undergo hypertrophy and lose their fundamental functions. (B) Comparison of ECM in healthy tissue and fibrotic tissue. In fibrotic tissue, abnormal fibroblasts and tissue inhibitor of metalloproteinases (TIMPs) increase, leading to collagen and proteoglycan deposition. (C) Diagram showing tumoral ECM, part of the TME. Here, CAFs trigger a marked rise in matrix components, especially adhesive glycoproteins like fibronectin. This action enhances the ability of tumor cells to adhere, migrate, and invade. (D) During the three stages of wound healing, the ECM undergoes significant changes. In the inflammatory phase, inflammatory factors and macrophages are the main components. During the proliferative phase, collagen and fibronectin…

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  Figure 3. Schematic illustration of glucocorticoids (GCs) signaling orchestrates the regulation of ECM through coordinated genomic and non-genomic mechanisms. The genomic pathway, mediated by cytosolic GR activation, involves ligand-dependent nuclear translocation and subsequent binding to GCs response elements (GREs) in promoter regions, thereby regulating transcriptional programs governing ECM biosynthesis and degradation. The non-genomic mechanisms manifest through rapid membrane-associated GR signaling, which initiates within seconds to minutes via kinase cascade activation, modulating ECM remodeling. By Figdraw (https://www.figdraw.com).

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  Figure 4. Schematic illustration of ECM across healthy, diseased, and treated states. The figure shows the effects of pathogenic factors and glucocorticoids (GCs) on ECM components, as well as the potential mechanisms of precision therapy. By Figdraw (https://www.figdraw.com).