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The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to alkalinization-induced vascular calcification in vitro.

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机构: [1]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, China
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关键词: alkalinization KCa3 1 Runx2 vascular calcification

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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-induced VSMCs calcification in vitro.Rat VSMCs calcification model was established by beta-glycerophosphate (β-GP, 10 mM) induction. The pH of Dulbecco's modified Eagle's medium (DMEM) was adjusted every 24 h with 10 mM HCl or 10 mM NaHCO3 . The mineralization was measured by Alizarin Red staining and O-cresolphthalein complex one method. mRNA and protein expression were detected by RT-PCR and Western blot or immunofluorescence. Ca2+ influx was measured by Elisa.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-related transcription factor 2 (Runx2). Blocking KCa3.1 with TRAM-34 or shRNA vector can significantly lowered the effects of calcification in the activity of ALP and Runx2 expression.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-34 and KCa3.1-shRNA ameliorated VSMCs calcification by downregulating KCa3.1.© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.

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出版当年[2021]版:
大类 | 4 区 医学
小类 | 4 区 医学实验技术
最新[2025]版:
大类 | 4 区 医学
小类 | 3 区 医学实验技术
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出版当年[2021]版:
Q2 MEDICAL LABORATORY TECHNOLOGY
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Q2 MEDICAL LABORATORY TECHNOLOGY

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第一作者机构: [1]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, China
通讯作者:
通讯机构: [1]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, China [*1]Department of Nephrology, the Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, China.
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