{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:16:38Z","timestamp":1785428198264,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003356","name":"Gazi University","doi-asserted-by":"publisher","award":["TDK-2023-8958"],"award-info":[{"award-number":["TDK-2023-8958"]}],"id":[{"id":"10.13039\/501100003356","id-type":"DOI","asserted-by":"publisher"}]},{"award":["TDK-2023-8958"],"award-info":[{"award-number":["TDK-2023-8958"]}],"id":[{"id":"https:\/\/ror.org\/054xkpr46","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: This study investigates the role of MMPs and TIMPs in sepsis pathogenesis. We aim to assess multiple potential biomarkers including MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-13, TIMP-1, TIMP-2, TIMP-3 in serum, brain and kidney tissue samples. To this date, there is not such extensive assessment of MMP and TIMP in sepsis pathogenesis. Methods: Experimental sepsis was generated using an LPS-induced endotoxemia model in rats. After 24 h, serum, brain and kidney samples were collected. Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-13, and TIMP-1, TIMP-2, TIMP-3 were measured by ELISA. Inflammatory cytokines (TNF-\u03b1, IL-6, IL-10, and IFN-\u03b3) were analyzed to assess the inflammatory response. Results: Analysis revealed that MMP-1 concentrations were elevated in kidney and brain tissues, as well as in serum in the sepsis group. MMP-2 levels exhibited statistically significant increases in brain tissues compared to controls. Elevations in MMP-3 were observed across brain, kidney and serum samples. MMP-8 levels were significantly increased in the serum. MMP-9 concentrations were higher in serum and kidney samples of septic rats compared with controls, while MMP-13 levels were elevated in kidney tissues of the sepsis group. TIMP measurements also revealed tissue-specific elevations in sepsis. TIMP-1 was significantly increased in kidney; TIMP-2 showed significant rises in brain tissue and serum; and TIMP-3 was markedly elevated in kidney tissues. Conclusions: A major strength of our study is the simultaneous assessment of multiple parameters. Our findings offer preliminary evidence of tissue-specific MMP and TIMP responses in sepsis and may guide future research exploring their biomarker potential. We anticipate that these results will inform both future clinical and pharmacological research and assist in the interpretation of subsequent studies.<\/jats:p>","DOI":"10.3390\/medsci14030370","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T07:59:47Z","timestamp":1783065587000},"page":"370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Matrix Metalloproteinases and Tissue Inhibitors in Sepsis Pathogenesis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8008-4712","authenticated-orcid":false,"given":"Rasime Sevgi","family":"Cenan","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Gazi University Hospital, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015feg\u00fcl","family":"Karao\u011flan","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Gazi University Hospital, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatice","family":"Pa\u015fao\u011flu","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Gazi University Hospital, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.5492\/wjccm.v12.i4.188","article-title":"Biomarkers in sepsis-looking for the Holy Grail or chasing a mirage!","volume":"12","author":"Ahuja","year":"2023","journal-title":"World J. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ventura, F., Greub, G., Liles, W.C., and Jacob, S.T. (2024). Proposed Framework for Conducting Clinically Relevant Translational Biomarker Research for the Diagnosis, Prognosis and Management of Sepsis. Diagnostics, 14.","DOI":"10.3390\/diagnostics14030300"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/s13054-024-05032-9","article-title":"Enhancing sepsis biomarker development: Key considerations from public and private perspectives","volume":"28","author":"Llitjos","year":"2024","journal-title":"Crit. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta19970","article-title":"Protocolised Management In Sepsis (ProMISe): A multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock","volume":"19","author":"Mouncey","year":"2015","journal-title":"Health Technol. Assess."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1097\/CCM.0000000000007089","article-title":"Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock","volume":"54","author":"Prescott","year":"2026","journal-title":"Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6","DOI":"10.4046\/trd.2018.0041","article-title":"Sepsis: Early Recognition and Optimized Treatment","volume":"82","author":"Kim","year":"2019","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_7","first-page":"18","article-title":"Epidemiology and prognostic factors in severe sepsis\/septic shock. Evolution over six years","volume":"40","author":"Choperena","year":"2016","journal-title":"Med. Intensiv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41581-019-0199-3","article-title":"Prognostic and predictive enrichment in sepsis","volume":"16","author":"Stanski","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/10408363.2013.764490","article-title":"Biomarkers of sepsis","volume":"50","author":"Faix","year":"2013","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vella, R., Panci, D., Carini, F., Malta, G., Vieni, S., David, S., Albano, G.D., Puntarello, M., Zerbo, S., and Argo, A. (2025). Cytokines in sepsis: A critical review of the literature on systemic inflammation and multiple organ dysfunction. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1682306"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"156006","DOI":"10.1016\/j.cyto.2022.156006","article-title":"Proinflammatory cytokines levels in sepsis and healthy volunteers, and tumor necrosis factor-alpha associated sepsis mortality: A systematic review and meta-analysis","volume":"158","author":"Gharamti","year":"2022","journal-title":"Cytokine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5557","DOI":"10.2147\/IDR.S384351","article-title":"Diagnostic and Prognostic Value of Interleukin-6 in Emergency Department Sepsis Patients","volume":"15","author":"Yu","year":"2022","journal-title":"Infect. Drug Resist."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"156056","DOI":"10.1016\/j.cyto.2022.156056","article-title":"Alterations in levels of cytokine following treatment to predict outcome of sepsis: A meta-analysis","volume":"161","author":"Li","year":"2023","journal-title":"Cytokine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s10753-026-02512-8","article-title":"The Dual Role of Interleukin-10 in Sepsis: Research Progress and Therapeutic Prospects","volume":"49","author":"Wang","year":"2026","journal-title":"Inflammation"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rosier, F., Nu\u00f1ez, N.F., Torres, M., Loriod, B., Rihet, P., and Pradel, L.C. (2022). Transcriptional Response in a Sepsis Mouse Model Reflects Transcriptional Response in Sepsis Patients. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020821"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1093\/ilar\/ilx007","article-title":"Murine Models of Sepsis and Trauma: Can We Bridge the Gap?","volume":"58","author":"Stortz","year":"2017","journal-title":"ILAR J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1097\/SHK.0000000000002742","article-title":"Optimization of Preclinical Rodent Research Models of Human Shock: Part One Intra-Abdominal Sepsis","volume":"65","author":"Rodhouse","year":"2026","journal-title":"Shock"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1515\/cclm-2014-0520","article-title":"Matrix metalloproteinases as biomarkers of disease: Updates and new insights","volume":"53","author":"Galliera","year":"2015","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1016\/j.bbamcr.2017.05.010","article-title":"Matrix metalloproteinases as regulators of inflammatory processes","volume":"1864","author":"Fingleton","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s12035-013-8433-7","article-title":"Matrix metalloproteinase-2 and metalloproteinase-9 activities are associated with blood-brain barrier dysfunction in an animal model of severe sepsis","volume":"48","author":"Rojas","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1097\/CCM.0b013e318232e404","article-title":"A novel role for matrix metalloproteinase-8 in sepsis","volume":"40","author":"Solan","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Alekhmimi, N.K., Raddadi, Z., Alabdulwahed, A.A., Eissa, S., Cialla-May, D., Popp, J., Al-Kattan, K., and Zourob, M. (2023). Paper-Based Biosensor for the Detection of Sepsis Using MMP-9 Biomarker in FIP Mice Model. Biosensors, 13.","DOI":"10.3390\/bios13080804"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Salom\u00e3o, R., Assis, V., de Sousa Neto, I.V., Petriz, B., Babault, N., Durigan, J.L.Q., and de C\u00e1ssia Marqueti, R. (2023). Involvement of Matrix Metalloproteinases in COVID-19: Molecular Targets, Mechanisms, and Insights for Therapeutic Interventions. Biology, 12.","DOI":"10.3390\/biology12060843"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1007\/s10517-023-05791-5","article-title":"Evaluation of the Efficiency of TIMP-2 as a Biomarker for Acute Kidney Injury in Sepsis","volume":"174","author":"Li","year":"2023","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1177\/0885066617732284","article-title":"Predictive Value of Matrix Metalloproteinases and Their Inhibitors for Mortality in Septic Patients: A Cohort Study","volume":"35","author":"McCosham","year":"2020","journal-title":"J. Intensive Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lorente, L., Mart\u00edn, M.M., Sol\u00e9-Viol\u00e1n, J., Blanquer, J., Labarta, L., D\u00edaz, C., Borreguero-Le\u00f3n, J.M., Orbe, J., Rodr\u00edguez, J.A., and Jim\u00e9nez, A. (2014). Association of sepsis-related mortality with early increase of TIMP-1\/MMP-9 ratio. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094318"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Forsblom, E., Tervahartiala, T., Ruotsalainen, E., J\u00e4rvinen, A., and Sorsa, T. (2021). Matrix metalloproteinase MMP-8, TIMP-1 and MMP-8\/TIMP-1 ratio in plasma in methicillin-sensitive Staphylococcus aureus bacteremia. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252046"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5064684","DOI":"10.1155\/2018\/5064684","article-title":"Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis after Major Abdominal Surgery","volume":"2018","author":"Bojic","year":"2018","journal-title":"Dis. Markers"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tiwary, S., O\u2019Neil, C.A., Lawless, S., Arter, O., Brown, M., Roemmich, B., Samuels, C., Kwon, J.H., and Farnsworth, C.W. (2026). Assessment of TIMP1, Transgelin-2, and Procalcitonin as Protein Biomarkers for Diagnosis and Prognosis of Bloodstream Infection in a Critically Ill Cohort. J. Appl. Lab. Med., jfag084.","DOI":"10.1093\/jalm\/jfag084"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/SHK.0000000000001833","article-title":"Elevated Plasma Levels of Matrix Metalloproteinase-3 and Tissue-Inhibitor of Matrix Metalloproteinases-1 Associate with Organ Dysfunction and Mortality in Sepsis","volume":"57","author":"Jones","year":"2022","journal-title":"Shock"}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/3\/370\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T09:18:51Z","timestamp":1783070331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/3\/370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":30,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["medsci14030370"],"URL":"https:\/\/doi.org\/10.3390\/medsci14030370","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]}}}