{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:54:26Z","timestamp":1791114866200,"version":"4.1.0"},"reference-count":82,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2001,3,1]]},"abstract":"<jats:p>The expansion of cysts in polycystic kidneys bears several similarities to the invasion of the extracellular matrix by benign tumors. We therefore hypothesized that cyst-lining epithelial cells produce extracellular matrix-degrading metalloproteinases and that the inhibition of these enzymes may represent a potential target for therapeutic intervention. Using in situ hybridization, we first analyzed the expression of membrane-type metalloproteinase 1 (MMP-14), an essential matrix metalloproteinase, of its inhibitor TIMP-2, and of the cytokine transforming growth factor (TGF)-\u03b22 in the ( cy\/ +) rat model of autosomal-dominant polycystic kidney disease. Upregulated MMP-14 mRNA was predominantly located in cyst-lining epithelia and distal tubules, whereas TIMP-2 mRNA was confined almost exclusively to fibroblasts. TGF-\u03b22, a cytokine known to regulate the expression of matrix metalloproteinases and their inhibitors, was also expressed by cyst wall epithelia. We then treated ( cy\/ +) rats with the metalloproteinase inhibitor batimastat for a period of 8 wk. The treatment with the metalloproteinase inhibitor batimastat resulted in a significant reduction of cyst number and kidney weight. Our study suggests that metalloproteinase inhibitors represent a new therapeutic tool against polycystic kidney disease, which should be applicable independently of the background of the disease.<\/jats:p>","DOI":"10.1152\/ajprenal.2001.280.3.f540","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T13:15:32Z","timestamp":1514034932000},"page":"F540-F550","source":"Crossref","is-referenced-by-count":65,"title":["A possible role for metalloproteinases in renal cyst development"],"prefix":"10.1152","volume":"280","author":[{"given":"Nicholas","family":"Oberm\u00fcller","sequence":"first","affiliation":[{"name":"Medical Research Center, Klinikum Mannheim, University of Heidelberg, 68167 Mannheim; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natividad","family":"Morente","sequence":"additional","affiliation":[{"name":"Medical Research Center, Klinikum Mannheim, University of Heidelberg, 68167 Mannheim; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Kr\u00e4nzlin","sequence":"additional","affiliation":[{"name":"Medical Research Center, Klinikum Mannheim, University of Heidelberg, 68167 Mannheim; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Gretz","sequence":"additional","affiliation":[{"name":"Medical Research Center, Klinikum Mannheim, University of Heidelberg, 68167 Mannheim; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Witzgall","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology I, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1681\/ASN.V102300","volume":"10","author":"Aukema HM","year":"1999","journal-title":"J Am Soc Nephrol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.358"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s004670050744"},{"key":"B5","first-page":"1899","volume":"4","author":"Beattie GJ","year":"1998","journal-title":"Clin Cancer Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/1359-6446(96)89115-X"},{"key":"B7","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1182\/blood.V81.12.3324.3324","volume":"81","author":"Benezra M","year":"1993","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(95)80116-2"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199411103311907"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/BF02990939"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1993.17"},{"key":"B12","first-page":"437","volume":"70","author":"Carone FA","year":"1994","journal-title":"Lab Invest"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1984.154"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(96)90525-9"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1993.79"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(97)90039-1"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6235"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1987.tb02449.x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(199911)21:11<940::AID-BIES6>3.0.CO;2-J"},{"key":"B21","doi-asserted-by":"crossref","first-page":"11951","DOI":"10.1016\/S0021-9258(19)50292-7","volume":"268","author":"Falcone DJ","year":"1993","journal-title":"J Biol Chem"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.195"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1991.87"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/0272-6386(95)90013-6"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/0272-6386(95)90497-2"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1995.319"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80064-1"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.6.1309"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.36.22389"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9531"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.6.F934"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(12)80907-3"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.9.5902"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.159"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.6.1363"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(97)90206-7"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.12.12.1075"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5266.1339"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(00)70330-1"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.31.21491"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1159\/000013552"},{"key":"B42","first-page":"88","volume":"3","author":"Norman JT","year":"1995","journal-title":"Exp Nephrol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1496"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1997.273.3.F357"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.274.3.F541"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00287.x"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00835.x"},{"key":"B48","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1681\/ASN.V661649","volume":"6","author":"Ogborn MR","year":"1995","journal-title":"J Am Soc Nephrol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/0272-6386(95)90059-4"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00205.x"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00975.x"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199010183231601"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.115.4.1091"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/47260"},{"key":"B55","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1681\/ASN.V102210","volume":"10","author":"Rankin CA","year":"1999","journal-title":"J Am Soc Nephrol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.383"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2071"},{"key":"B58","first-page":"345","volume":"376","author":"Ries C","year":"1995","journal-title":"Biol Chem Hoppe-Seyler"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1997.272.1.F139"},{"key":"B60","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1242\/dev.124.13.2659","volume":"124","author":"Sanford LP","year":"1997","journal-title":"Development"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.10"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1994.253"},{"key":"B63","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1242\/dev.111.1.117","volume":"111","author":"Schmid P","year":"1991","journal-title":"Development"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(97)00125-0"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s004670050376"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.275.3.F387"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00829.x"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00577.x"},{"key":"B69","doi-asserted-by":"crossref","first-page":"25378","DOI":"10.1016\/S0021-9258(19)74051-4","volume":"267","author":"Taipale J","year":"1992","journal-title":"J Biol Chem"},{"key":"B70","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1681\/ASN.V971242","volume":"9","author":"Tanner GA.","year":"1998","journal-title":"J Am Soc Nephrol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199809)213:1<121::AID-AJA12>3.0.CO;2-5"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90137-6"},{"key":"B73","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1681\/ASN.V5122037","volume":"5","author":"The Modification of Diet in Renal Disease Study Group","year":"1995","journal-title":"J Am Soc Nephrol"},{"key":"B74","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1681\/ASN.V561355","volume":"5","author":"Tomobe K","year":"1994","journal-title":"J Am Soc Nephrol"},{"key":"B75","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1681\/ASN.V551193","volume":"5","author":"Torres VE","year":"1994","journal-title":"J Am Soc Nephrol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81169-1"},{"key":"B77","first-page":"3629","volume":"55","author":"Watson SA","year":"1995","journal-title":"Cancer Res"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1997.272.4.F434"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005722729132"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/368750a0"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.222"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1021\/jm970404a"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.060037197"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.2001.280.3.F540","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T03:42:42Z","timestamp":1660189362000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.2001.280.3.F540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,3,1]]},"references-count":82,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2001,3,1]]}},"alternative-id":["10.1152\/ajprenal.2001.280.3.F540"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.2001.280.3.f540","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,3,1]]}}}