{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nWNT9A is a secreted glycoprotein whose evolutionarily conserved coding region underscores its pivotal roles in diverse developmental processes. In the kidney, increased WNT9A expression promotes tubular epithelial cell senescence and activates fibroblasts, thereby driving renal fibrosis through β‐catenin and TGF‐β1 signaling cascades."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " During craniofacial development, WNT9A is required for palatal extension by guiding chondrocyte proliferation and intercalation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", while in hematopoiesis it signals via the Fzd9b receptor—with a necessary role for EGFR as a cofactor—to amplify blood progenitor cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Comparative genomics studies have revealed a high degree of amino acid conservation in WNT9A, although divergence in regulatory promoter regions may underpin species-specific regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in the developing auditory organ of birds, restricted expression of WNT9A along the neural edge is essential for proper radial patterning and cell fate determination of sensory hair cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant WNT9A activity also appears to contribute to a variety of pathological states. In colonic epithelial cells, exposure to the food additive carrageenan or reductions in arylsulfatase B activity enhance WNT9A expression, promoting β‐catenin activation and altering transcription through mechanisms involving galectin‑3 and Sp1; these events may mediate inflammatory changes and predispose to polyp formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " Elevated WNT9A expression is also noted in certain hematologic malignancies such as chronic lymphocytic leukemia"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and has been shown to modulate cellular proliferation in breast cancer cells, where overexpression inhibits growth while knockdown promotes proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In inflammatory conditions, WNT9A influences cytokine and growth factor networks: its increased production in synovial fibroblasts contributes to rheumatoid arthritis pathology by modulating both canonical Wnt/β‑catenin signaling and noncanonical pathways such as p38 and NFκB"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and its upregulation in flexor tenosynovium correlates with enhanced VEGF expression in idiopathic carpal tunnel syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Additionally, genetic studies have linked WNT9A variants to late‑onset acute respiratory distress syndrome"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "and thumb osteoarthritis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", while its expression in various tumors further underscores a context‐dependent involvement in oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Congwei Luo, Shan Zhou, Zhanmei Zhou, et al. 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