{"doi":"10.1002/cbf.2932","title":"Augmentation of <i>ADAMTS9</i> gene expression by IL‐1<i>β</i> is reversed by NF<i>κ</i>B and MAPK inhibitors, but not PI3 kinase inhibitors","abstract":"<jats:p>The pathways involved in the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated. Therefore, the aim of this study was to investigate the involvement of nuclear factor‐<jats:italic>κ</jats:italic>B (NF‐<jats:italic>κ</jats:italic>B), mitogen activated protein kinases (MAPK) and Phosphatidylinositol 3‐kinase (PI3 kinase) in <jats:italic>ADAMTS9</jats:italic> gene regulation, with special focus on the involvement of NF‐<jats:italic>κ</jats:italic>B in IL‐1<jats:italic>β</jats:italic>‐induced ADAMTS9 expression. The OUMS‐27 chondrosarcoma cells were exposed to IL‐1<jats:italic>β</jats:italic>. They were pretreated with 20 μM PD98059 (specific inhibitor of p44/42 kinase), 10 μM SB203580 (specific inhibitor of p38 kinase), 20 μM SB600125 (MAPK inhibitor), and 1 μM Wortmannin and 10 μM LY294002 (specific inhibitors of PI3 kinase) for 30 min and subsequently incubated with IL‐1<jats:italic>β</jats:italic>. For the effects of NF‐<jats:italic>κ</jats:italic>B and I<jats:italic>κ</jats:italic>B inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL‐1<jats:italic>β</jats:italic>. BAY117085 and different concentrations of curcumin were applied to the cells just after the first experiment to determine their concentration effect on <jats:italic>ADAMTS9</jats:italic> gene expression. After total RNA was extracted, they were reversely transcribed with random primers and then real‐time polymerase chain reaction (PCR) was performed on cDNA samples.</jats:p><jats:p>There was a significant difference between control and stimulated cells in terms of ADAMTS9/<jats:italic>β</jats:italic>‐actin ratio. Wortmannin and LY294002 did not have any repressive effect on the OUMS‐27 whereas SB203580 and SP600125 were found to decrease the expression of <jats:italic>ADAMTS9</jats:italic> gene. BAY 117085 and curcumin, which are two NF‐<jats:italic>κ</jats:italic>B inhibitors, led to a decrease in the ratio of ADAMTS9/<jats:italic>β</jats:italic>‐actin. As a conclusion, the pathways MAPK and NF‐<jats:italic>κ</jats:italic>B were thought to be responsible pathways for the induction of <jats:italic>ADAMTS9</jats:italic> gene. Copyright © 2012 John Wiley &amp; Sons, Ltd.</jats:p>","journal":"Cell Biochemistry and Function","year":2013,"id":655451,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1711062,"name":"Zahide Nur Ünal","orcid":null,"position":1,"is_corresponding":false},{"id":1711063,"name":"Serpil Erdoğan","orcid":null,"position":2,"is_corresponding":false},{"id":409495,"name":"Sümeyya Akyol","orcid":"0000-0003-4845-1620","position":3,"is_corresponding":false},{"id":1711065,"name":"M. Ramazan Yiğitoğlu","orcid":null,"position":4,"is_corresponding":false},{"id":1711066,"name":"Satoshi Hirohata","orcid":null,"position":5,"is_corresponding":false},{"id":1711067,"name":"Bünyamin Işık","orcid":null,"position":6,"is_corresponding":false},{"id":1711068,"name":"Kadir Demircan","orcid":null,"position":7,"is_corresponding":false},{"id":1711061,"name":"Sema Uysal","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Augmentation of <i>ADAMTS9</i> gene expression by IL‐1<i>β</i> is reversed by NF<i>κ</i>B and MAPK inhibitors, but not PI3 kinase inhibitors","abstract":"<jats:p>The pathways involved in the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated. Therefore, the aim of this study was to investigate the involvement of nuclear factor‐<jats:italic>κ</jats:italic>B (NF‐<jats:italic>κ</jats:italic>B), mitogen activated protein kinases (MAPK) and Phosphatidylinositol 3‐kinase (PI3 kinase) in <jats:italic>ADAMTS9</jats:italic> gene regulation, with special focus on the involvement of NF‐<jats:italic>κ</jats:italic>B in IL‐1<jats:italic>β</jats:italic>‐induced ADAMTS9 expression. The OUMS‐27 chondrosarcoma cells were exposed to IL‐1<jats:italic>β</jats:italic>. They were pretreated with 20 μM PD98059 (specific inhibitor of p44/42 kinase), 10 μM SB203580 (specific inhibitor of p38 kinase), 20 μM SB600125 (MAPK inhibitor), and 1 μM Wortmannin and 10 μM LY294002 (specific inhibitors of PI3 kinase) for 30 min and subsequently incubated with IL‐1<jats:italic>β</jats:italic>. For the effects of NF‐<jats:italic>κ</jats:italic>B and I<jats:italic>κ</jats:italic>B inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL‐1<jats:italic>β</jats:italic>. BAY117085 and different concentrations of curcumin were applied to the cells just after the first experiment to determine their concentration effect on <jats:italic>ADAMTS9</jats:italic> gene expression. After total RNA was extracted, they were reversely transcribed with random primers and then real‐time polymerase chain reaction (PCR) was performed on cDNA samples.</jats:p><jats:p>There was a significant difference between control and stimulated cells in terms of ADAMTS9/<jats:italic>β</jats:italic>‐actin ratio. Wortmannin and LY294002 did not have any repressive effect on the OUMS‐27 whereas SB203580 and SP600125 were found to decrease the expression of <jats:italic>ADAMTS9</jats:italic> gene. BAY 117085 and curcumin, which are two NF‐<jats:italic>κ</jats:italic>B inhibitors, led to a decrease in the ratio of ADAMTS9/<jats:italic>β</jats:italic>‐actin. As a conclusion, the pathways MAPK and NF‐<jats:italic>κ</jats:italic>B were thought to be responsible pathways for the induction of <jats:italic>ADAMTS9</jats:italic> gene. Copyright © 2012 John Wiley &amp; Sons, Ltd.</jats:p>","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23175174","pmcid":null,"openalex_id":"https://openalex.org/W2143106426","authors":[],"funders":[],"total_grants":0,"fwci":1.2543,"citation_percentile":0.76658604,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":2},{"year":2014,"count":1},{"year":2015,"count":4},{"year":2016,"count":2},{"year":2017,"count":2},{"year":2019,"count":1},{"year":2020,"count":4},{"year":2022,"count":1},{"year":2025,"count":3}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcbf.2932","host_type":"publisher"},{"url":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cbf.2932","host_type":"publisher"},{"url":"https://doi.org/10.1002/cbf.2932","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23175174","host_type":"repository"}],"fields_of_study":["Cell Adhesion Molecules Research","NF-κB Signaling Pathways","Angiogenesis and VEGF in Cancer","ADAM Proteins","ADAMTS9 Protein","Gene Expression Regulation","Humans","Interleukin-1beta","Mitogen-Activated Protein Kinase Kinases","NF-kappa B","Phosphatidylinositol 3-Kinases","Phosphoinositide-3 Kinase Inhibitors","Tumor Cells, Cultured"],"mesh_terms":["ADAMTS9 Protein","Phosphoinositide-3 Kinase Inhibitors","Gene Expression Regulation","Humans","Tumor Cells, Cultured","NF-kappa B","Phosphatidylinositol 3-Kinases","Mitogen-Activated Protein Kinase Kinases","ADAM Proteins","Interleukin-1beta"],"keywords":["Wortmannin","LY294002","Kinase","MAPK/ERK pathway","Molecular biology","Phosphatidylinositol","Biology","p38 mitogen-activated protein kinases","Gene expression","PI3K/AKT/mTOR pathway","Cell biology","Signal transduction","Gene","Biochemistry","Inhibitors","MAPK","Curcumin","Aggrecan","Pi3 Kinase","Nfκb","Adamts9","Bay117085"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T10:59:45.882228Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}