Expression patterns, features and roles of SRPX2 in disease pathogenesis
KeAi Communications Co., Ltd.Peer-Reviewed Publication
SRPX2 is a chondroitin sulfate proteoglycan (CSPG) exhibiting significant N-glycosylation, which influences its conformation, interactions, and functions, as evidenced by the enhanced glycosylation and functional impact of the N327S mutation. It plays versatile roles in multiple diseases. SRPX2 promotes cancer progression (e.g., gastric, pancreatic, thyroid, glioblastoma) by enhancing proliferation, migration, invasion, and chemoresistance via pathways like TGF-β, PI3K/AKT, Wnt/β-catenin, and FAK/SRC/ERK, correlating with poor prognosis. SRPX2 also plays critical roles in neurodevelopment; mutations are linked to language disorders, autism spectrum disorder (ASD), and potentially Rolandic epilepsy (though evidence is complex and may involve interactions like GRIN2A). SRPX2, a protein characterized by sushi repeat domains, plays a crucial role in synaptogenesis and modulates complement-mediated synaptic pruning processes. Additionally, SRPX2 contributes to idiopathic pulmonary fibrosis via TGF-β signaling, angiogenesis via μPAR/integrin signaling, myocardial infarction protection by inhibiting PI3K/AKT/mTOR, and other conditions. Its context-dependent roles, e.g., pro-fibrotic in lungs vs. protective in heart, and involvement in key signaling pathways highlight its potential as a therapeutic target, though challenges like inhibitor specificity remain.
- Journal
- Glycoscience & Therapy
- Funder
- National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, Suzhou Medical and Health Technology Innovation Project, Clinical Research Center of Neurological Disease in The Second Affiliated Hospital of Soochow University, State Key Laboratory of Drug Research, Young Science Talents Promotion Project of Jiangsu Science and Technology Association, Jiangsu Shuangchuang Program for Doctor, Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases, the Priority Academic Program Development of Jiangsu Higher Education Institutes (PAPD), Project of MOE Key Laboratory of Geriatric Diseases and Immunology, Postgraduate Research & Practice Innovation Program of Jiangsu Province