{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:57:31Z","timestamp":1791644251494,"version":"4.3.4"},"reference-count":75,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ruhr-Universit\u00e4t Bochum"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Ectopic calcification and dysregulated extracellular matrix remodeling are prominent hallmarks of the complex heterogenous pathobiochemistry of pseudoxanthoma elasticum (PXE). The disease arises from mutations in ABCC6, an ATP-binding cassette transporter expressed predominantly in the liver. Neither its substrate nor the mechanisms by which it contributes to PXE are completely understood. The fibroblasts isolated from PXE patients and Abcc6\u2212\/\u2212 mice were subjected to RNA sequencing. A group of matrix metalloproteinases (MMPs) clustering on human chromosome 11q21-23, respectively, murine chromosome 9, was found to be overexpressed. A real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescent staining confirmed these findings. The induction of calcification by CaCl2 resulted in the elevated expression of selected MMPs. On this basis, the influence of the MMP inhibitor Marimastat (BB-2516) on calcification was assessed. PXE fibroblasts (PXEFs) exhibited a pro-calcification phenotype basally. PXEF and normal human dermal fibroblasts responded with calcium deposit accumulation and the induced expression of osteopontin to the addition of Marimastat to the calcifying medium. The raised MMP expression in PXEFs and during cultivation with calcium indicates a correlation of ECM remodeling and ectopic calcification in PXE pathobiochemistry. We assume that MMPs make elastic fibers accessible to controlled, potentially osteopontin-dependent calcium deposition under calcifying conditions.<\/jats:p>","DOI":"10.3390\/biom13040672","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T02:29:15Z","timestamp":1681352955000},"page":"672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Matrix Metalloproteinases Contribute to the Calcification Phenotype in Pseudoxanthoma Elasticum"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-9415","authenticated-orcid":false,"given":"Ricarda","family":"Pl\u00fcmers","sequence":"first","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lindenkamp","sequence":"additional","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel Robin","family":"Osterhage","sequence":"additional","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius","family":"Knabbe","sequence":"additional","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3660-6923","authenticated-orcid":false,"given":"Doris","family":"Hendig","sequence":"additional","affiliation":[{"name":"Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut f\u00fcr Laboratoriums- und Transfusionsmedizin, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, Georgstra\u00dfe 11, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1365-4362.1988.tb01280.x","article-title":"Pseudoxanthoma elasticum","volume":"27","author":"Neldner","year":"1988","journal-title":"Int. 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