{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:07:53Z","timestamp":1790172473692,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>In order to find new strategies for the prevention of vascular calcification in uremic individuals especially treated by dialysis and develop novel therapeutic targets in vascular calcification, we explore the role of KCa3.1 in alkalinization\u2010induced VSMCs calcification in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Rat VSMCs calcification model was established by beta\u2010glycerophosphate (\u03b2\u2010GP, 10\u00a0mM) induction. The pH of Dulbecco's modified Eagle's medium (DMEM) was adjusted every 24\u00a0h with 10\u00a0mM HCl or 10\u00a0mM\u00a0NaHCO\n                      <jats:sub>3<\/jats:sub>\n                      . The mineralization was measured by Alizarin Red staining and O\u2010cresolphthalein complex one method. mRNA and protein expression were detected by RT\u2010PCR and Western blot or immunofluorescence. Ca2+ influx was measured by Elisa.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>The results indicated that alkalization induced an increase in Ca2+ influx to enhance VSMCs calcification. Furthermore, the increase of calcification was associated with the expression of KCa3.1 via advanced expression of osteoblastic differentiation markers alkaline phosphatase (ALP) and Runt\u2010related transcription factor 2 (Runx2). Blocking KCa3.1 with TRAM\u201034 or shRNA vector can significantly lowered the effects of calcification in the activity of ALP and Runx2 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together all, our studies suggested that alkalinization can promote vascular calcification by upregulating KCa3.1 channel and enhancing osteogenic\/chondrogenic differentiation by upregulating Runx2. The specific inhibitor TRAM\u201034 and KCa3.1\u2010shRNA ameliorated VSMCs calcification by downregulating KCa3.1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcla.23854","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T06:39:01Z","timestamp":1627367941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The intermediate\u2010conductance calcium\u2010activated potassium channel KCa3.1 contributes to alkalinization\u2010induced vascular calcification in vitro"],"prefix":"10.1002","volume":"35","author":[{"given":"Yaling","family":"Bai","sequence":"first","affiliation":[{"name":"Hebei Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Departments of Nephrology The Fourth Hospital of Hebei Medical University Shijiazhuang 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