{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:42:51Z","timestamp":1787506971785,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FORUM Research Grant of the Ruhr-University Bochum","award":["K107-16"],"award-info":[{"award-number":["K107-16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pseudoxanthoma elasticum (PXE) is a rare autosomal-recessive disorder that is mainly caused by mutations in the ATP-binding cassette sub-family C member 6 (ABCC6) gene. Clinically PXE is characterized by a loss of skin elasticity, arteriosclerosis or visual impairments. It also shares some molecular characteristics with known premature aging syndromes like the Hutchinson\u2013Gilford progeria syndrome (HGPS). However, little is known about accelerated aging processes, especially on a cellular level for PXE now. Therefore, this study was performed to reveal a potential connection between premature cellular aging and PXE pathogenesis by analyzing cellular senescence, a corresponding secretory phenotype and relevant factors of the cell cycle control in primary human dermal fibroblasts of PXE patients. Here, we could show an increased senescence-associated \u03b2-galactosidase (SA-\u03b2-Gal) activity as well as an increased expression of proinflammatory factors of a senescence-associated secretory phenotype (SASP) like interleukin 6 (IL6) and monocyte chemoattractant protein-1 (MCP1). We further observed an increased gene expression of the cyclin-dependent kinase inhibitor (CDKI) p21, but no simultaneous induction of p53 gene expression. These data indicate that PXE is associated with premature cellular senescence, which is possibly triggered by a p53-independent p21-mediated mechanism leading to a proinflammatory secretory phenotype.<\/jats:p>","DOI":"10.3390\/ijms21249665","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T11:42:09Z","timestamp":1608291729000},"page":"9665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Linking ABCC6 Deficiency in Primary Human Dermal Fibroblasts of PXE Patients to p21-Mediated Premature Cellular Senescence and the Development of a Proinflammatory Secretory Phenotype"],"prefix":"10.3390","volume":"21","author":[{"given":"Janina","family":"Tiemann","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lindenkamp","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-9415","authenticated-orcid":false,"given":"Ricarda","family":"Pl\u00fcmers","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2234-9196","authenticated-orcid":false,"given":"Isabel","family":"Faust","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius","family":"Knabbe","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 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":"Institut f\u00fcr Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum Nordrhein-Westfalen, Universit\u00e4tsklinik der Ruhr-Universit\u00e4t Bochum, 32545 Bad Oeynhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13023-017-0639-8","article-title":"Pseudoxanthoma elasticum","volume":"12","author":"Germain","year":"2017","journal-title":"Orphanet J. 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