{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T23:13:27Z","timestamp":1788563607355,"version":"build-2803163510"},"reference-count":39,"publisher":"Georg Thieme Verlag KG","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heart and Stroke Foundation of\n                        Canada","award":["G-24-0036367"],"award-info":[{"award-number":["G-24-0036367"]}]},{"name":"Medical Research Fund of the Affiliated Qingyuan Hospital of\n                        Guangzhou Medical University, Qingyuan People\u2019s Hospital","award":["No. 15001019001289"],"award-info":[{"award-number":["No. 15001019001289"]}]},{"name":"Natural Science Foundation of\n                        Guangdong Province","award":["No. 2023A1515010295"],"award-info":[{"award-number":["No. 2023A1515010295"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Matrix metalloproteinases play critical roles in wound repair, yet their\n                    context-dependent functions in diabetic wound healing remain elusive. In this\n                    study, we found that both the expression and activity of matrix\n                    metalloproteinase-14 were significantly elevated in diabetic foot ulcers. Using\n                    animal models, we further revealed the dual roles of matrix metalloproteinase-14\n                    in wound healing. In normal rats, inhibition of matrix metalloproteinase-14\n                    delayed wound closure, confirming its supportive role in physiological tissue\n                    repair. In contrast, in diabetic rats, pathologically increased matrix\n                    metalloproteinase-14 levels impaired healing, whereas moderate inhibition\n                    significantly accelerated wound repair. Among the inhibitors tested, the\n                    selective matrix metalloproteinase-14 inhibitor NSC405020 produced the most\n                    favorable therapeutic effect in diabetic wounds, markedly enhancing healing\n                    rates and collagen deposition at a concentration of 1 mg\/mL. Compared with the\n                    broad-spectrum matrix metalloproteinase inhibitor ND336, NSC405020 demonstrated\n                    therapeutic safety and comparable efficacy without notable toxicity in a rat\n                    model. Collectively, these findings elucidate the context-dependent role of\n                    matrix metalloproteinase-14 in wound healing, suggesting that matrix\n                    metalloproteinase-14 may be a promising therapeutic target for diabetic wound\n                    healing. Therefore, our study provides a theoretical foundation for the\n                    development of effective and safe treatments for diabetic wound management.<\/jats:p>","DOI":"10.1055\/a-2943-8604","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T23:39:58Z","timestamp":1787355598000},"source":"Crossref","is-referenced-by-count":0,"title":["The Effects of matrix metalloproteinase-14 Inhibition on\n                    diabetic Wound Healing"],"prefix":"10.1055","author":[{"given":"Gui-feng","family":"Zeng","sequence":"first","affiliation":[{"name":"Affiliated Qingyuan Hospital (Qingyuan People's\n                    Hospital), Guangzhou Medical University, Guangdong Province, China","place":["Qingyuan"],"department":["Department of Orthopedics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guotian","family":"Chen","sequence":"first","affiliation":[{"name":"Affiliated Qingyuan Hospital (Qingyuan People's\n                    Hospital), Guangzhou Medical University, Guangdong Province, China","place":["Qingyuan"],"department":["Department of Orthopedics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhou","sequence":"first","affiliation":[{"name":"Affiliated Nanhua Hospital, Nanhua\n                    University, Hunan, China","place":["Hengyang"],"department":["Health Management Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shui-lan","family":"Zou","sequence":"first","affiliation":[{"name":"Affiliated Qingyuan Hospital (Qingyuan People's\n                    Hospital), Guangzhou Medical University, Guangdong Province, China","place":["Qingyuan"],"department":["Department of Gynaecology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-guang","family":"Chen","sequence":"additional","affiliation":[{"name":"Affiliated Qingyuan Hospital (Qingyuan People's\n                    Hospital), Guangzhou Medical University, Guangdong Province, China","place":["Qingyuan"],"department":["Department of Orthopedics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Qingyuan Hospital (Qingyuan People's\n                    Hospital), Guangzhou Medical University, Guangdong Province, China","place":["Qingyuan"],"department":["Department of Orthopedics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Affiliated Qingyuan Hospital (Qingyuan People's\n                    Hospital), Guangzhou Medical University, Guangdong Province, China","place":["Qingyuan"],"department":["Department of Orthopedics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-hong","family":"Pan","sequence":"additional","affiliation":[{"name":"Affiliated Qingyuan Hospital (Qingyuan People's\n                    Hospital), Guangzhou Medical University, Guangdong Province, China","place":["Qingyuan"],"department":["Department of Orthopedics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Affiliated Qingyuan Hospital (Qingyuan People's\n                    Hospital), Guangzhou Medical University, Guangdong Province, China","place":["Qingyuan"],"department":["Department of Orthopedics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Affiliated Qingyuan Hospital (Qingyuan People's\n                    Hospital), Guangzhou Medical University, Guangdong Province, China","place":["Qingyuan"],"department":["Department of Orthopedics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Alberta, Alberta, Canada","place":["Edmonton"],"department":["Department of Pediatrics and Group on the Molecular and Cell Biology of\n                    Lipids"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1318-3745","authenticated-orcid":false,"given":"Xiao-dan","family":"Xia","sequence":"additional","affiliation":[{"name":"Affiliated Qingyuan Hospital (Qingyuan People's\n                    Hospital), Guangzhou Medical University, Guangdong Province, China","place":["Qingyuan"],"department":["Department of Orthopedics"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"issue":"24","key":"ref1","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1056\/NEJMra1615439","article-title":"Diabetic foot ulcers and their recurrence","volume":"376","author":"D G Armstrong","year":"2017","journal-title":"N Engl J Med"},{"issue":"05","key":"ref2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1089\/wound.2021.0026","article-title":"Human wound and Its Burden: Updated 2020 compendium of estimates","volume":"10","author":"C K Sen","year":"2021","journal-title":"Adv Wound Care"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for\n                    2030 and 2045: Results from the International Diabetes Federation Diabetes\n                    Atlas, 9th edition","volume":"157","author":"P Saeedi","year":"2019","journal-title":"Diabetes Res Clin Pract"},{"issue":"04","key":"ref4","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1515\/jbcpp-2020-0502","article-title":"Cost of illness of diabetes mellitus in Indonesia: A systematic review","volume":"32","author":"Y F Patty","year":"2021","journal-title":"J Basic Clin Physiol Pharmacol"},{"issue":"01","key":"ref5","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1001\/jama.2023.10578","article-title":"Diabetic foot ulcers: A review","volume":"330","author":"D G Armstrong","year":"2023","journal-title":"JAMA."},{"issue":"03","key":"ref6","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3390\/cells10030655","article-title":"Chronic diabetic wounds and their treatment with skin substitutes","volume":"10","author":"J Holl","year":"2021","journal-title":"Cells"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.2147\/IJN.S363827","article-title":"Efficiency of multifunctional antibacterial hydrogels for chronic wound healing\n                    in diabetes: A comprehensive review","volume":"17","author":"J Y Ji","year":"2022","journal-title":"Int J Nanomedicine"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s10787-023-01407-6","article-title":"Insights into the mechanisms of diabetic wounds: pathophysiology, molecular\n                    targets, and treatment strategies through conventional and alternative\n                    therapies","volume":"32","author":"J P Yadav","year":"2024","journal-title":"Inflammopharmacology."},{"key":"ref9","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1395479","article-title":"Recent advances in molecular mechanisms of skin wound healing and its\n                    treatments","volume":"15","author":"A A Mamun","year":"2024","journal-title":"Front Immunol"},{"issue":"04","key":"ref10","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a041243","article-title":"Molecular pathophysiology of chronic wounds: Current state and future\n                    directions","volume":"15","author":"I Pastar","year":"2023","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"07","key":"ref11","first-page":"4391","article-title":"Role of matrix metalloproteinase in wound healing","volume":"14","author":"M Kandhwal","year":"2022","journal-title":"Am J Transl Res"},{"issue":"06","key":"ref12","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1111\/wrr.13218","article-title":"Single-cell RNA-seq in diabetic foot ulcer wound healing","volume":"32","author":"Y Dong","year":"2024","journal-title":"Wound Repair Regener"},{"issue":"11","key":"ref13","first-page":"111400","article-title":"Crosstalk between oxidative stress and inflammatory pathways: Natural\n                    therapeutic approaches for diabetic wound healing","volume":"16","author":"Y L Guo","year":"2025","journal-title":"World J Diabetes"},{"issue":"10","key":"ref14","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.3390\/medicina57101072","article-title":"Diabetic wound-healing science","volume":"57","author":"J L Burgess","year":"2021","journal-title":"Medicina"},{"issue":"05","key":"ref15","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1021\/acs.accounts.0c00864","article-title":"Strategy for treatment of infected diabetic foot ulcers","volume":"54","author":"M Chang","year":"2021","journal-title":"Acc Chem Res"},{"issue":"24","key":"ref16","doi-asserted-by":"crossref","first-page":"13691","DOI":"10.3390\/ijms252413691","article-title":"The complex role of matrix metalloproteinase-2 (MMP-2) in health and\n                    disease","volume":"25","author":"M Wolosowicz","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref17","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.1050630","article-title":"Role of matrix metalloproteinases in diabetic foot ulcers: Potential therapeutic\n                    targets","volume":"13","author":"K Fu","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref18","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2025.1517519","article-title":"Potential target within the tumor microenvironment - MT1-MMP","volume":"16","author":"J Liu","year":"2025","journal-title":"Front Immunol"},{"issue":"18","key":"ref19","doi-asserted-by":"crossref","first-page":"6917","DOI":"10.1073\/pnas.0305862101","article-title":"Membrane protease proteomics: Isotope-coded affinity tag MS identification of\n                    undescribed MT1-matrix metalloproteinase substrates","volume":"101","author":"E M Tam","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.matbio.2023.10.002","article-title":"Mmp14 is required for matrisome homeostasis and circadian rhythm in\n                    fibroblasts","volume":"124","author":"C Y Yeung","year":"2023","journal-title":"Matrix biology"},{"issue":"03","key":"ref21","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.3390\/ijms24032183","article-title":"The role of membrane-type 1 matrix metalloproteinase-substrate interactions in\n                    pathogenesis","volume":"24","author":"H Lee","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"03","key":"ref22","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3390\/cells14030209","article-title":"The diverse pathways for cell surface MT1-MMP localization in migratory\n                    cells","volume":"14","author":"H Kelly","year":"2025","journal-title":"Cells."},{"issue":"04","key":"ref23","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1007\/s11010-022-04372-w","article-title":"Clinically relevant experimental rodent models of diabetic foot ulcer","volume":"477","author":"V Rai","year":"2022","journal-title":"Mol Cell Biochem"},{"issue":"04","key":"ref24","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/wrr.12717","article-title":"Metalloproteinases in chronic and acute wounds: A systematic review and\n                    meta-analysis","volume":"27","author":"A Tard\u00e1guila-Garc\u00eda","year":"2019","journal-title":"Wound Repair Regener"},{"issue":"01","key":"ref25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jtv.2022.12.001","article-title":"Effect of matrix metalloproteinases on the healing of diabetic foot ulcer: A\n                    systematic review","volume":"32","author":"W Q Zhang","year":"2023","journal-title":"J Tissue Viability"},{"issue":"09","key":"ref26","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s00403-014-1494-2","article-title":"Expression and vitamin D-mediated regulation of matrix metalloproteinases (MMPs)\n                    and tissue inhibitors of metalloproteinases (TIMPs) in healthy skin and in\n                    diabetic foot ulcers","volume":"306","author":"N L\u00f3pez-L\u00f3pez","year":"2014","journal-title":"Arch Dermatol Res"},{"issue":"07","key":"ref27","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s00125-002-0868-8","article-title":"Expression of matrix-metalloproteinases and their inhibitors in the wounds of\n                    diabetic and non-diabetic patients","volume":"45","author":"R Lobmann","year":"2002","journal-title":"Diabetologia"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.msec.2018.05.020","article-title":"Effect of biogenic silver nanocubes on matrix metalloproteinases 2 and 9\n                    expressions in hyperglycemic skin injury and its impact in early wound healing\n                    in streptozotocin-induced diabetic mice","volume":"91","author":"N Krishnan","year":"2018","journal-title":"Mater Sci Eng C"},{"issue":"06","key":"ref29","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00403-009-1011-1","article-title":"Protease and pro-inflammatory cytokine concentrations are elevated in chronic\n                    compared to acute wounds and can be modulated by collagen type I in vitro","volume":"302","author":"C Wiegand","year":"2010","journal-title":"Arch Dermatol Res"},{"issue":"01","key":"ref30","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1021\/cb4005468","article-title":"A chemical biological strategy to facilitate diabetic wound healing","volume":"9","author":"M Gooyit","year":"2014","journal-title":"ACS Chem Biol"},{"issue":"01","key":"ref31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1021\/acsptsci.0c00104","article-title":"Selective MMP-9 Inhibitor (R)-ND-336 alone or in combination with linezolid\n                    accelerates wound healing in infected diabetic mice","volume":"4","author":"Z Peng","year":"2020","journal-title":"ACS Pharmacol Transl Sci"},{"issue":"01","key":"ref32","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3390\/ijms23010146","article-title":"Matrix metalloproteinases shape the tumor microenvironment in cancer\n                    progression","volume":"23","author":"S Niland","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"04","key":"ref33","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1083\/jcb.200405001","article-title":"MT1-MMP-dependent neovessel formation within the confines of the\n                    three-dimensional extracellular matrix","volume":"167","author":"T H Chun","year":"2004","journal-title":"J Cell Biol"},{"issue":"02","key":"ref34","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1097\/00006534-200002000-00024","article-title":"Differential expression of matrix metalloproteinases and their tissue-derived\n                    inhibitors in cutaneous wound repair","volume":"105","author":"C Soo","year":"2000","journal-title":"Plastic Reconstructive Surg"},{"issue":"49","key":"ref35","doi-asserted-by":"crossref","first-page":"15226","DOI":"10.1073\/pnas.1517847112","article-title":"Acceleration of diabetic wound healing using a novel protease-anti-protease\n                    combination therapy","volume":"112","author":"M Gao","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"09","key":"ref36","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1158\/0008-5472.CAN-11-4149","article-title":"Novel MT1-MMP small-molecule inhibitors based on insights into hemopexin domain\n                    function in tumor growth","volume":"72","author":"A G Remacle","year":"2012","journal-title":"Cancer Res"},{"issue":"01","key":"ref37","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40942-022-00394-0","article-title":"Comparison of matrix metalloproteinase 9 and 14 levels in vitreous samples in\n                    diabetic and non-diabetic patients: A case control study","volume":"8","author":"A \u00dcnal","year":"2022","journal-title":"Int J Retina Vitreous"},{"issue":"11","key":"ref38","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/s41581-021-00462-y","article-title":"Trajectories of kidney function in diabetes: a clinicopathological update","volume":"17","author":"M Oshima","year":"2021","journal-title":"Nat Rev Nephrol"},{"issue":"10","key":"ref39","doi-asserted-by":"crossref","first-page":"884","DOI":"10.3390\/bios12100884","article-title":"Detecting the PEX Like domain of matrix metalloproteinase-14 (MMP-14) with\n                    therapeutic conjugated CNTs","volume":"12","author":"D Vieira","year":"2022","journal-title":"Biosensors"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2943-8604.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:37:50Z","timestamp":1788561470000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2943-8604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":39,"URL":"https:\/\/doi.org\/10.1055\/a-2943-8604","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8,21]]},"published":{"date-parts":[[2026,8,21]]}}}