Fibroblast activation protein (FAP) promotes cardiac fibroblast activation in association with impaired ER-phagy

Figures

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  Figure 1. Conceptual framework linking diabetes-associated hPTM dysregulation to impaired immune resolution and tissue repair. The pathways shown are selected representative mechanisms and are not intended to provide an exhaustive summary of all histone post-translational modification (hPTM)-related pathways discussed in the manuscript. Under physiological conditions, apoptotic neutrophil clearance and local tissue-derived signals support dynamic changes across a macrophage-state continuum, including inflammatory or injury-responsive, intermediate or adaptive, and reparative or pro-resolution states. These states are functional descriptors rather than discrete or terminal M1/M2 lineages. Their relative abundance and activities may vary with wound-healing stage, anatomical location and microenvironment. In diabetic wounds, hyperglycemia, advanced glycation end products (AGEs), palmitate, oxidative stress and inflammatory mediators may disturb macrophage signaling and hPTM regulation. Representative mechanisms include MLL1-associated H3K4me3 enrichment, palmitate–TLR4/MyD88–JMJD3 signaling with reduced H3K27me3, TNF-alpha–MOF/KAT8-associated H4K16ac, dysregulated STAT3–SETDB2 signaling,…

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  Figure 2. Stages of normal cutaneous wound healing and the major cellular events. Wound healing proceeds through four stages: hemostasis, inflammation, proliferation, and remodeling, which are sequentially connected and partially overlap in time. During hemostasis, platelets aggregate and form a fibrin clot, while damage-associated molecular patterns (DAMPs) initiate the local inflammatory response. During inflammation, neutrophils and monocytes are recruited to the wound, and macrophages acquire temporally and spatially distinct inflammatory, reparative and intermediate functional states that contribute to inflammation resolution and tissue repair. The proliferative phase is characterized primarily by angiogenesis, fibroblast activation, extracellular matrix (ECM) deposition, and re-epithelialization. The remodeling phase involves myofibroblast contraction, collagen fiber reorganization, and ECM maturation. Arrows indicate the relationships among the major cellular and tissue repair events. ROS, reactive oxygen species; NETs, neutrophil extracellular traps; SPMs, specialized pro-resolving mediators; VEGF, vascular endothelial growth factor; TGF-β, transforming growth factor-β; PDGF,…