{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:48:52Z","timestamp":1792082932008,"version":"4.4.0"},"reference-count":40,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Fistulae are a troublesome complication of Crohn\u2019s disease but little is known of the final effector molecules responsible for matrix degradation. Although matrix metalloproteinases (MMPs) have been strongly implicated in tissue injury in Crohn\u2019s disease, their role in fistula formation is unknown.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aim:<\/jats:bold>\n                    To determine the expression pattern of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in fistulae of patients with Crohn\u2019s disease.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Patients and methods:<\/jats:bold>\n                    Resected fistula specimens were obtained from patients with Crohn\u2019s disease (n\u200a=\u200a11) and classified according to the predominant histological features\u2014that is, acute versus chronic inflammation. Patients with fistulae due to other diseases (n\u200a=\u200a9) and normal colon (n\u200a=\u200a5) served as controls. MMP and TIMP protein expression was measured by single or double labelled immunohistochemistry, and mRNA expression by in situ hybridisation. MMP activity was measured by gelatin zymography.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Compared with normal colon, strong MMP-3 expression was consistently observed in fistulae in Crohn\u2019s disease, irrespective of the stage of inflammatory activity. MMP-3 transcripts and protein were localised in large mononuclear cells and fibroblasts. MMP-9 transcripts and protein were expressed in granulocytes and only in fistulae with acute inflammation. Staining for MMP-1 and MMP-7 was weak and negative for MMP-10, whereas MMP-2 was equally expressed in normal colon and fistulae. TIMP-1, TIMP-2, and TIMP-3 expression was low in all samples. Similar expression patterns were found in fistulae of the disease control group. Fistulae also expressed active MMP-2 and MMP-9, as measured by gelatin zymography.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    MMP-3 and MMP-9 are markedly upregulated in intestinal fistulae and may contribute to fistula formation through degradation of the extracellular matrix, irrespective of the underlying disease process.\n                  <\/jats:p>","DOI":"10.1136\/gut.2003.017442","type":"journal-article","created":{"date-parts":[[2004,4,13]],"date-time":"2004-04-13T18:28:16Z","timestamp":1081880896000},"page":"701-709","source":"Crossref","is-referenced-by-count":196,"title":["Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn\u2019s disease"],"prefix":"10.1136","volume":"53","author":[{"given":"T","family":"Kirkegaard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Bruun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Brynskov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2004,4,13]]},"reference":[{"key":"2025120520103200000_53.5.701.1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32362"},{"key":"2025120520103200000_53.5.701.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199905063401804"},{"key":"2025120520103200000_53.5.701.3","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.24884"},{"key":"2025120520103200000_53.5.701.4","first-page":"iv2","volume":"49","year":"2002","journal-title":"Gut"},{"key":"2025120520103200000_53.5.701.5","doi-asserted-by":"publisher","DOI":"10.1097\/00054725-200203000-00007"},{"key":"2025120520103200000_53.5.701.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020831"},{"key":"2025120520103200000_53.5.701.7","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.35393"},{"key":"2025120520103200000_53.5.701.8","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/00054725-200002000-00002","volume":"6","year":"2000","journal-title":"Inflamm Bowel Dis"},{"key":"2025120520103200000_53.5.701.9","first-page":"55","volume":"266","year":"1995","journal-title":"Acta Orthop Scand Suppl"},{"key":"2025120520103200000_53.5.701.10","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(90)90126-Q"},{"key":"2025120520103200000_53.5.701.11","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1200\/JCO.2000.18.5.1135","volume":"18","year":"2000","journal-title":"J Clin Oncol"},{"key":"2025120520103200000_53.5.701.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70339-2"},{"key":"2025120520103200000_53.5.701.13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb11139.x"},{"key":"2025120520103200000_53.5.701.14","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2001.01142.x"},{"key":"2025120520103200000_53.5.701.15","doi-asserted-by":"publisher","DOI":"10.1136\/gut.47.1.63"},{"key":"2025120520103200000_53.5.701.16","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01227.x"},{"key":"2025120520103200000_53.5.701.17","doi-asserted-by":"publisher","DOI":"10.1136\/gut.47.1.57"},{"key":"2025120520103200000_53.5.701.18","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.47.2.113"},{"key":"2025120520103200000_53.5.701.19","first-page":"519","volume":"148","year":"1996","journal-title":"Am J Pathol"},{"key":"2025120520103200000_53.5.701.20","first-page":"1005","volume":"152","year":"1998","journal-title":"Am J Pathol"},{"key":"2025120520103200000_53.5.701.21","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.4049\/jimmunol.158.4.1582","volume":"158","year":"1997","journal-title":"J Immunol"},{"key":"2025120520103200000_53.5.701.22","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3109\/00365529209000127","volume":"27","year":"1992","journal-title":"Scand J Gastroenterol"},{"key":"2025120520103200000_53.5.701.23","unstructured":"Cotan RS, Kumar V, Collins TC. 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