{"@type": "dcat:Dataset", "accessLevel": "public", "bureauCode": ["009:25"], "contactPoint": {"@type": "vcard:Contact", "fn": "NIH", "hasEmail": "mailto:info@nih.gov"}, "description": "Background\n          Functional antagonism between transforming growth factor beta (TGF-\u03b2) and hyaluronidase has been demonstrated. For example, testicular hyaluronidase PH-20 counteracts TGF-\u03b21-mediated growth inhibition of epithelial cells. PH-20 sensitizes various cancer cells to tumor necrosis factor (TNF) cytotoxicity by upregulating proapoptotic p53 and WW domain-containing oxidoreductase (WOX1). TGF-\u03b21 blocks PH-20-increased TNF cytotoxicity. In the present study, the functional antagonism between TGF-\u03b21 and lysosomal hyaluronidases Hyal-1 and Hyal-2 was examined.\n        \n        \n          Results\n          Murine L929 fibroblasts were engineered to stably express green-fluorescent protein (GFP)-tagged hyaluronidase (GFP-Hyal-1 or GFP-Hyal-2) or GFP alone. Compared to control cells, Hyal-2-expressing cells had a significantly increased sensitivity to TNF cytotoxicity (~60\u2013110% increase), while Hyal-1-expressing cells were less sensitive to TNF (~20\u201390% increase). TNF activated NF-\u03baB, along with I\u03baB\u03b1 degradation, occurred at 20 to 60 min in Hyal-2 cells post stimulation, but at the 20 min time point in both control and Hyal-1 cells. Hyal-2 cells, but not Hyal-1 and control cells, constitutively expressed WOX1, and transiently expressed Hyal-2 enhanced WOX1-mediated cell death. Unlike PH-20, Hyal-1 and Hyal-2 did not induce p53 expression. Hyal-2 translocated from the lysosome to the mitochondria during staurosporine-mediated apoptosis, suggesting that Hyal-2 may damage mitochondria. Finally, Hyal-1 and Hyal-2 blocked TGF-\u03b21-enhanced L929 cell growth. In contrast, TGF-\u03b21 inhibited Hyal-1- and Hyal-2-increased TNF cytotoxicity in L929 cells by 30\u201350%.\n        \n        \n          Conclusions\n          TGF-\u03b21 limits the ability of Hyal-2 to induce TNF cytotoxicity in L929 cells. Hyal-2-increased TNF cytotoxicity in L929 cells appears to be correlated with upregulation of WOX1, a prolonged NF-\u03baB activation, and Hyal-2 translocation to the mitochondria during apoptosis.", "distribution": [{"@type": "dcat:Distribution", "description": "Visit the original government dataset for complete information, documentation, and data access.", "downloadURL": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC102332/", "mediaType": "text/html", "title": "Official Government Data Source"}], "identifier": "https://healthdata.gov/api/views/afbn-mcya", "issued": "2025-07-14", "keyword": ["hyaluronidase-hyal-2", "l929-fibroblasts", "nih", "tnf-cytotoxicity", "transforming-growth-factor"], "landingPage": "https://healthdata.gov/d/afbn-mcya", "modified": "2025-09-06", "programCode": ["009:033"], "publisher": {"@type": "org:Organization", "name": "National Institutes of Health"}, "theme": ["NIH"], "title": "Transforming growth factor-\u03b21 blocks the enhancement of tumor necrosis factor cytotoxicity by hyaluronidase Hyal-2 in L929 fibroblasts"}