{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:33:29Z","timestamp":1787697209395,"version":"build-2784847793"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1\u201015\u2010ACN\u201006"],"award-info":[{"award-number":["1\u201015\u2010ACN\u201006"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetic foot ulcers are characterized by hypoxia. For many patients, hyperbaric oxygen (HBO) therapy is the last recourse for saving the limb from amputation, for which the molecular basis is not understood. We previously identified the active form of matrix metalloproteinase\u20109 (MMP\u20109) as responsible for diabetic foot ulcer's recalcitrance to healing. Transcription of <jats:italic>mmp\u20109<\/jats:italic> to the inactive zymogen is upregulated during hypoxia. Activation of the zymogen is promoted by proteases and reactive oxygen species (ROS). We hypothesized that the dynamics of these two events might lead to a lowering of active MMP\u20109 levels in the wounded tissue. We employed the full\u2010thickness excisional <jats:italic>db\/db<\/jats:italic> mouse model to study wound healing, and treated the mice to 3.0\u2009atm of molecular oxygen for 90\u2009minutes, 5\u2009days per week for 10\u2009days in an HBO research chamber. Treatment with HBO accelerated diabetic wound healing compared to untreated mice, with more completed and extended reepithelialization. We imaged the wounds for ROS in vivo with a luminol\u2010based probe and found that HBO treatment actually decreases ROS levels. The levels of superoxide dismutase, catalase, and glutathione peroxidase\u2014enzymes that turn over ROS\u2014increased after HBO treatment, hence the observation of decreased ROS. Since ROS levels are lowered, we explored the effect that this would have on activation of MMP\u20109. Quantitative analysis with an affinity resin that binds and pulls down the active MMPs exclusively, coupled with proteomics, revealed that HBO treatment indeed reduces the active MMP\u20109 levels. This work for the first time demonstrates that diminution of active MMP\u20109 is a contributing factor and a mechanism for enhancement of diabetic wound healing by HBO therapy.<\/jats:p>","DOI":"10.1111\/wrr.12782","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T06:39:11Z","timestamp":1574059151000},"page":"194-201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Hyperbaric oxygen therapy accelerates wound healing in diabetic mice by decreasing active matrix metalloproteinase\u20109"],"prefix":"10.1111","volume":"28","author":[{"given":"Trung T.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Notre Dame  Notre Dame Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5940-2448","authenticated-orcid":false,"given":"Jeffrey 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