{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Gastrointestinal glutathione peroxidase 2 (GPX2) is a selenoenzyme that plays a dual role in the maintenance of mucosal homeostasis and in modulating tumor biology. In normal gut epithelium, GPX2 is expressed predominantly in crypt cells where it is transcriptionally induced by electrophilic compounds via an antioxidant response element (ARE)–dependent mechanism regulated by Nrf2."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " By reducing hydroperoxides and thereby limiting reactive oxygen species (ROS), GPX2 protects intestinal epithelial cells from oxidative injury and inflammation, as evidenced by the severe ileocolitis and predisposition to bacteria‐associated inflammation and cancer observed in mice lacking both GPX2 and its related isoenzyme GPX1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, GPX2 expression is upregulated in response to oxidative stresses such as cigarette smoke in lung epithelium, further underscoring its role as an inducible antioxidant."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the context of tumorigenesis, GPX2 appears to have a “Janus-faced” function. While its cytoprotective action helps maintain redox balance and limits inflammation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", experimental knockdown of GPX2 in colon cancer cells reduces anchorage‐independent growth and tumor weight yet paradoxically enhances cell migration and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, additional evidence suggests that modulation of GPX2 expression may impact mitochondrial antioxidant enzyme profiles and redox signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Together, these findings illustrate that GPX2 is critical for counteracting oxidative stress in the gastrointestinal tract by scavenging hydroperoxides, thereby preventing inflammation‐induced mucosal damage and influencing the balance between cell survival and malignancy.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Antje Banning, Stefanie Deubel, Dirk Kluth, et al. 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