{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:08:47Z","timestamp":1787015327813,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T00:00:00Z","timestamp":1502064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004043","name":"Kanazawa Medical University","doi-asserted-by":"publisher","award":["SR 2013\u20132015"],"award-info":[{"award-number":["SR 2013\u20132015"]}],"id":[{"id":"10.13039\/501100004043","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2017,12]]},"abstract":"Abstract<\/jats:title>\n \n Connective tissue growth factor (\n CTGF<\/jats:styled-content>\n ) is involved in inflammation, pathogenesis and progression of liver fibrosis. Matrix metalloproteinase\u201013 (\n MMP<\/jats:styled-content>\n \u201013) cleaves\n CTGF<\/jats:styled-content>\n and releases several fragments, which are more potent than the parent molecule to induce fibrosis. The current study was aimed to elucidate the significance of\n MMP<\/jats:styled-content>\n \u201013 and\n CTGF<\/jats:styled-content>\n and their downstream effects in liver injury and fibrosis. Hepatic fibrosis was induced using intraperitoneal injections of\n N<\/jats:italic>\n \u2010nitrosodimethylamine (\n NDMA<\/jats:styled-content>\n ) in doses of 10 \u03bcg\/g body weight on three consecutive days of each week over a period of 4 weeks in both wild\u2010type (\n WT<\/jats:styled-content>\n ) and\n MMP<\/jats:styled-content>\n \u201013 knockout mice. Administration of\n NDMA<\/jats:styled-content>\n resulted in marked elevation of\n AST<\/jats:styled-content>\n ,\n ALT<\/jats:styled-content>\n ,\n TGF<\/jats:styled-content>\n \u2010\u03b21 and hyaluronic acid in the serum and activation of stellate cells, massive necrosis, deposition of collagen fibres and increase in total collagen in the liver of\n WT<\/jats:styled-content>\n mice with a significant decrease in\n MMP<\/jats:styled-content>\n \u201013 knockout mice. Protein and\n mRNA<\/jats:styled-content>\n levels of\n CTGF<\/jats:styled-content>\n ,\n TGF<\/jats:styled-content>\n \u2010\u03b21, \u03b1\u2010\n SMA<\/jats:styled-content>\n and type I collagen and the levels of\n MMP<\/jats:styled-content>\n \u20102,\n MMP<\/jats:styled-content>\n \u20109 and cleaved products of\n CTGF<\/jats:styled-content>\n were markedly increased in\n NDMA<\/jats:styled-content>\n \u2010treated\n WT<\/jats:styled-content>\n mice compared to the\n MMP<\/jats:styled-content>\n \u201013 knockout mice. Blocking of\n MMP<\/jats:styled-content>\n \u201013 with\n CL<\/jats:styled-content>\n \u201082198 in hepatic stellate cell cultures resulted in marked decrease of the staining intensity of\n CTGF<\/jats:styled-content>\n as well as protein levels of full\u2010length\n CTGF<\/jats:styled-content>\n and its C\u2010terminal fragments and active\n TGF<\/jats:styled-content>\n \u2010\u03b21. The data demonstrate that\n MMP<\/jats:styled-content>\n \u201013 and\n CTGF<\/jats:styled-content>\n play a crucial role in modulation of fibrogenic mediators and promote hepatic fibrogenesis. Furthermore, the study suggests that blocking of\n MMP<\/jats:styled-content>\n \u201013 and\n CTGF<\/jats:styled-content>\n has potential therapeutic implications to arrest liver fibrosis.\n <\/jats:p>","DOI":"10.1111\/jcmm.13304","type":"journal-article","created":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T03:22:48Z","timestamp":1502076168000},"page":"3821-3835","source":"Crossref","is-referenced-by-count":55,"title":["MMP<\/scp>\n \u201013 deletion decreases profibrogenic molecules and attenuates\n N<\/i>\n \u2010nitrosodimethylamine\u2010induced liver injury and fibrosis in mice"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5354-7884","authenticated-orcid":false,"given":"Joseph","family":"George","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Molecular Medicine College of Physicians and Surgeons Columbia University New York NY USA"},{"name":"Department of Hepatology Kanazawa Medical University Uchinada 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