{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:03:08Z","timestamp":1790244188329,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T00:00:00Z","timestamp":1506297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vascular calcification plays a role in the pathogenesis of atherosclerosis, diabetes, and chronic kidney disease; however, the role of apurinic\/apyrimidinic endonuclease 1\/redox factor-1 (APE1\/Ref-1) in inorganic phosphate (Pi)-induced vascular smooth muscle cell (VSMC) calcification remains unknown. In this study, we investigated the possible role of APE1\/Ref-1 in Pi-induced VSMC calcification. We observed that Pi decreased endogenous APE1\/Ref-1 expression and promoter activity in VSMCs, and that adenoviral overexpression of APE1\/Ref-1 inhibited Pi-induced calcification in VSMCs and in an ex vivo organ culture of a rat aorta. However, a redox mutant of APE1\/Ref-1(C65A\/C93A) did not reduce Pi-induced calcification in VSMCs, suggesting APE1\/Ref-1-mediated redox function against vascular calcification. Additionally, APE1\/Ref-1 overexpression inhibited Pi-induced intracellular and mitochondrial reactive oxygen species production, and APE1\/Ref-1 overexpression resulted in decreased Pi-induced lactate dehydrogenase activity, pro-apoptotic Bax levels, and increased anti-apoptotic Bcl-2 protein levels. Furthermore, APE1\/Ref-1 inhibited Pi-induced osteoblastic differentiation associated with alkaline phosphatase activity and inhibited Pi-exposure-induced loss of the smooth muscle phenotype. Our findings provided valuable insights into the redox function of APE1\/Ref-1 in preventing Pi-induced VSMC calcification by inhibiting oxidative stress and osteoblastic differentiation, resulting in prevention of altered osteoblastic phenotypes in VSMCs.<\/jats:p>","DOI":"10.3390\/ijms18102053","type":"journal-article","created":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T04:28:01Z","timestamp":1506400081000},"page":"2053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["APE1\/Ref-1 Inhibits Phosphate-Induced Calcification and Osteoblastic Phenotype Changes in Vascular Smooth Muscle Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Ki","family":"Lee","sequence":"first","affiliation":[{"name":"Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee","family":"Joo","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myoung","family":"Park","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuk-Seong","family":"Kim","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3358-7923","authenticated-orcid":false,"given":"Sunga","family":"Choi","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0763-4754","authenticated-orcid":false,"given":"Jin-Ok","family":"Jeong","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3347-2739","authenticated-orcid":false,"given":"Byeong","family":"Jeon","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/ndt\/gfg414","article-title":"Arterial media calcification in end-stage renal disease: Impact on all-cause and cardiovascular mortality","volume":"18","author":"London","year":"2003","journal-title":"Nephrol. 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