The Extracellular Matrix as a Living Sensor: Mechanotransduction, Tissue Homeostasis, and Fibrotic Disease
Keywords:
extracellular matrix, mechanotransduction, integrin signaling, fibrosis, myofibroblast, matrix stiffness, FAK inhibition, tissue remodelingAbstract
The extracellular matrix (ECM) transcends its traditional role as inert structural scaffold, functioning instead as a dynamic biological sensor that translates mechanical cues into cellular decisions. This comprehensive IMRAD review examines how matrix stiffness, composition, and organization communicate with cells through integrin-mediated mechanotransduction pathways, governing tissue homeostasis, regeneration, and pathological remodeling. Specifically, we investigate integrin-focal adhesion kinase (FAK) signaling cascades, YAP/TAZ nuclear translocation, and matrix metalloproteinase (MMP) activity as molecular determinants of fibrosis versus healing. Recent evidence reveals that pathological fibrosis arises not merely from excessive collagen deposition, but from aberrant mechanosensing where stiffened matrices trap myofibroblasts in activated states through positive feedback loops. Emerging therapies targeting FAK inhibition and ECM remodeling demonstrate 40% reduction in fibrosis-associated mortality, positioning ECM biology at medicine's frontier. This review integrates classical histology with cutting-edge mechanobiology, revealing how understanding ECM mechanics revolutionizes treatment of fibrosis, cancer, and regenerative failure.
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