<p>Pathological fibrosis is a chronic process characterized by excessive deposition of extracellular matrix (ECM), which disrupts tissue architecture and function and accelerates disease progression in organs such as the lungs, liver, heart, kidneys, skin, and eyes. Recent studies have identified leucine-rich α-2 glycoprotein-1 (LRG1), a secreted glycoprotein known for modulating angiogenesis and immune responses, as a key player in the pathogenesis of fibrotic disorders. LRG1 expression is up-regulated by multiple pro-fibrotic mediators, including transforming growth factor-beta (TGF-β), and has been shown to regulate fibroblast differentiation, myofibroblast activation, and ECM production. Through interactions with the TGF-β signaling pathway and other cascades, LRG1 plays a crucial role in pathological fibrosis. Elucidating the molecular mechanisms by which LRG1 drives fibrogenic responses will pave the way for novel therapeutic strategies targeting pathological fibrosis. This review explores the emerging functions of LRG1 in fibrosis of different organs and discusses therapeutic approaches aimed at mitigating fibrosis through LRG1 inhibition.</p>

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The critical role of LRG1 in pathological fibrosis

  • Tianxiang Yang,
  • Heping Xu

摘要

Pathological fibrosis is a chronic process characterized by excessive deposition of extracellular matrix (ECM), which disrupts tissue architecture and function and accelerates disease progression in organs such as the lungs, liver, heart, kidneys, skin, and eyes. Recent studies have identified leucine-rich α-2 glycoprotein-1 (LRG1), a secreted glycoprotein known for modulating angiogenesis and immune responses, as a key player in the pathogenesis of fibrotic disorders. LRG1 expression is up-regulated by multiple pro-fibrotic mediators, including transforming growth factor-beta (TGF-β), and has been shown to regulate fibroblast differentiation, myofibroblast activation, and ECM production. Through interactions with the TGF-β signaling pathway and other cascades, LRG1 plays a crucial role in pathological fibrosis. Elucidating the molecular mechanisms by which LRG1 drives fibrogenic responses will pave the way for novel therapeutic strategies targeting pathological fibrosis. This review explores the emerging functions of LRG1 in fibrosis of different organs and discusses therapeutic approaches aimed at mitigating fibrosis through LRG1 inhibition.