{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Leucine‐rich α2‐glycoprotein 1 (LRG1) is emerging as a multifunctional regulator that links inflammatory cues, aberrant angiogenesis, and tumor progression. Studies have demonstrated that LRG1 modulates transforming growth factor–β (TGF‐β) signaling—by binding accessory receptors such as endoglin—to promote pathogenic angiogenesis in ocular disease and diabetic kidney injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Inflammatory cytokines including interleukin‐6 and tumor necrosis factor–α induce LRG1 expression, positioning it as an acute‐phase protein and a marker of early neutrophilic differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the oncologic arena, elevated LRG1 has been observed in various human cancers—it promotes epithelial‐to‐mesenchymal transition (EMT), enhances cellular migration and invasion, and stimulates angiogenesis through pathways such as MAPK/p38 and HIF–1α, as reported in colorectal, gastric, pancreatic, and thyroid carcinomas."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": " Consistent with its functional roles, LRG1 is elevated in several biofluids—including serum, urine, and sputum—and serves as a sensitive biomarker for diseases such as non–small cell lung cancer, colorectal and pancreatic cancer, ulcerative colitis, rheumatoid arthritis, and even asthma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": " Beyond its roles in inflammation and cancer, LRG1 influences vascular homeostasis by affecting endothelial cell function and neovessel formation in conditions such as peripheral arterial disease, post‐stroke remodeling, and myocardial infarction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": " Moreover, LRG1 interacts with cytochrome c, thereby exerting a protective, anti–apoptotic effect on lymphocytes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " It also modulates immune cell signaling—for example, by upregulating IL-6 receptor expression to promote Th17 differentiation in rheumatoid arthritis—and links mechanical stimuli to angiogenic responses in skin fibrosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " Finally, tumor‐derived signals can systemically induce LRG1 expression in endothelial cells, thereby preconditioning distant vascular niches to favor metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "26"}]}, {"type": "t", "text": " Collectively, the diverse roles of LRG1—in mediating TGF‐β signaling, modulating inflammatory and angiogenic pathways, and promoting tumor progression—underscore its promise as both a diagnostic biomarker and a therapeutic target across a spectrum of diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiaomeng Wang, Sabu Abraham, Jenny A G McKenzie, et al. 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