{"corpus_id":232135609,"paper_sha":"88e95d658165cbb9c1ebf04562cc3c40c6faf6c1","doi":"10.1016/j.yexcr.2021.112550","arxiv_id":null,"pmid":33675806,"pmcid":null,"mag_id":3135766566,"dblp_id":null,"acl_id":null,"title":"High Glucose Activates ERK1/2 to Stabilize AP1 and Increase MMP9 Expression in Diabetic Foot Ulcers.","year":2021,"publication_date":"2021-03-03","venue":"Experimental Cell Research","journal":{"name":"Experimental cell research","pages":"\n          112550\n        ","volume":null},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":22,"citation_count":19,"influential_citation_count":0,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Diabetes Mellitus","mj":false,"qs":[{"q":"drug therapy","mj":false,"ui":"Q000188"}],"ui":"D003920"},{"d":"Diabetic Foot","mj":false,"qs":[{"q":"drug therapy","mj":true,"ui":"Q000188"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D017719"},{"d":"Glucose","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D005947"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"JNK Mitogen-Activated Protein Kinases","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D048031"},{"d":"MAP Kinase Signaling System","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D020935"},{"d":"Matrix Metalloproteinase 9","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D020780"},{"d":"Mitogen-Activated Protein Kinases","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D020928"},{"d":"Rats, Sprague-Dawley","mj":false,"ui":"D017207"},{"d":"Signal Transduction","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D015398"},{"d":"Transcription Factor AP-1","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D018808"},{"d":"Up-Regulation","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D015854"},{"d":"Rats","mj":false,"ui":"D051381"}],"chemicals":[{"n":"Transcription Factor AP-1","ui":"D018808","reg":"0"},{"n":"JNK Mitogen-Activated Protein Kinases","ui":"D048031","reg":"EC 2.7.11.24"},{"n":"Mitogen-Activated Protein Kinases","ui":"D020928","reg":"EC 2.7.11.24"},{"n":"Matrix Metalloproteinase 9","ui":"D020780","reg":"EC 3.4.24.35"},{"n":"Glucose","ui":"D005947","reg":"IY9XDZ35W2"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Increased matrix metalloproteinase 9 (MMP9) expression is involved in delayed wound healing in diabetic foot ulcers. We created skin wounds in normal SD rats and STZ-induced diabetic SD rats, then we found protein levels of activator protein-1 (AP1), a crucial transcription factor to increase MMP9 transcription, as well as MMP9 was up-regulated in epithelium of diabetic skin tissues. Then, we evaluated the mRNA and protein stability of AP1 subunits C-FOS/C-Jun in HaCaT cells after high glucose treatment. Results showed that high glucose could increase protein stability of C-FOS and C-Jun. Additionally, high glucose also activated extracellular signaling-related kinase 1/2 (ERK1/2). ERK1/2 inhibitor could rescue phosphorylation of C-FOS and C-Jun, increased protein stability of C-Jun, and increased MMP9 expressions. Thus, our study demonstrated that high glucose could activate ERK1/2 to stabilize AP1 and increase MMP9 expression in diabetic skin and HaCaT cells.","claims":[{"public_id":"cl_de62c6f1029cf4eb060b62759cde16b6","status":"active","text":"AP1 and MMP9 are up-regulated in the epithelium of diabetic skin tissues.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_de62c6f1029cf4eb060b62759cde16b6"},{"public_id":"cl_0c0263f44f30c3b24e63dd39082b2041","status":"active","text":"ERK1/2 inhibition rescues phosphorylation of C-FOS and C-Jun and increases protein stability of C-Jun while increasing MMP9 expression.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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