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Activated fibroblasts and myofibroblasts are specialized mesenchymal cells that play a central role in tissue repair and pathological fibrosis (Hinz et al., 2007, PubMed: 17664315). Upon injury or stimulation by growth factors like TGF-β, quiescent fibroblasts undergo a phenotypic transition into activated myofibroblasts, characterized by the expression of alpha-smooth muscle actin (α-SMA) and increased contractile capacity (Gabbiani, 2003, PubMed: 12928694). These cells are the primary producers of extracellular matrix (ECM) components, such as collagen and fibronectin, and they secrete various cytokines and growth factors that modulate the microenvironment (Wynn, 2008, PubMed: 18846103). In chronic diseases, persistent activation leads to excessive ECM deposition, resulting in organ dysfunction and fibrosis across the lung, liver, and kidney (Rockey et al., 2015, PubMed: 25830682). In oncology, cancer-associated fibroblasts (CAFs) contribute to tumor growth, immunosuppression, and drug resistance (Sahai et al., 2020, PubMed: 31900450). Therapeutic strategies targeting these cells include inhibiting activation pathways like TGF-β or PDGF signaling (e.g., Nintedanib), or direct depletion using cell-surface markers like Fibroblast Activation Protein (FAP) (Lindner et al., 2019, PubMed: 31171636).
Inhibition of pro-fibrotic signaling pathways (TGF-beta, PDGF, FGF), direct depletion of activated cell populations via surface markers (e.g., FAP), and inhibition of extracellular matrix cross-linking enzymes.
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