{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNote: Although none of the provided abstracts mention SCPEP1, they uniformly focus on the functions of SOX18—a member of the SOXF transcription factor family—and its closely related partners. In developmental models, SOX18 acts as a pivotal transcriptional switch that drives endothelial cell differentiation and lymphatic vasculogenesis. By directly activating key target genes (for example, Prox1), and by functioning in coordination with SOX7 and SOX17, SOX18 is essential for proper cardiovascular patterning; genetic ablation or dominant‐negative mutations in SOX18 lead to striking lymphatic and vascular defects in both mice and humans."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn pathological settings, SOX18 is re‐expressed or dysregulated in a manner that influences vascular integrity and remodeling. For instance, in tumor xenograft studies SOX18 reactivation supports tumor‐induced lymphangiogenesis and metastasis, while in models of acute inflammation its downregulation correlates with impaired endothelial barrier function owing to reduced tight junction (e.g., CLDN5) expression. Moreover, specific features of SOX18 such as its capacity to form dimers through a novel C‐terminal motif appear to refine its target gene selection during vascular remodeling and regeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in vascular development and barrier maintenance, SOX18 influences a broader range of processes. It contributes to the differentiation of hair follicle dermal papillae and modulates muscle satellite cell quiescence and renewal, thereby affecting postnatal muscle growth and regeneration. In airway smooth muscle, SOX18 regulates proliferation and migration via Notch1 signaling, implicating it in airway remodeling during conditions such as asthma. Furthermore, aberrant SOX18 activity can compromise epidermal adhesion by disrupting hemidesmosome formation. Complementary studies even hint at connections between regulatory circuits involving microRNA function and proteolytic enzymes (e.g. cathepsin A) with the signaling milieu in which SOX18 operates."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Neville Young, Christopher N Hahn, Alisa Poh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of disrupted SOX18 transcription factor function on tumor growth, vascularization, and endothelial development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Natl Cancer Inst (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jnci/djj299"}], "href": "https://doi.org/10.1093/jnci/djj299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16882943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16882943"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Toshiyasu Matsui, Masami Kanai-Azuma, Kenshiro Hara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.03081"}], "href": "https://doi.org/10.1242/jcs.03081"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16895970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16895970"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Youhei Sakamoto, Kenshiro Hara, Masami Kanai-Azuma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Redundant roles of Sox17 and Sox18 in early cardiovascular development of mouse embryos."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2007.06.093"}], "href": "https://doi.org/10.1016/j.bbrc.2007.06.093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17610846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17610846"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mathias François, Andrea Caprini, Brett Hosking, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sox18 induces development of the lymphatic vasculature in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature07391"}], "href": "https://doi.org/10.1038/nature07391"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18931657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18931657"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Meredith Downes, Mathias François, Charles Ferguson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp219"}], "href": "https://doi.org/10.1093/hmg/ddp219"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19429912"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19429912"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Brett Hosking, Mathias François, Dagmar Wilhelm, et al. 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