Dexamethasone increases αvβ3 integrin expression and affinity through a calcineurin/NFAT pathway.
Dexamethasone increases αvβ3 integrin expression and affinity through a calcineurin/NFAT pathway.
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DOI：
10.1016/j.bbamcr.2013.09.020
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发表时间：
2013-12
影响因子：
5.1
通讯作者：
Peters, Donna M.
中科院分区：
文献类型：
--
作者：
Faralli, Jennifer A.;Gagen, Debjani;Filla, Mark S.;Crotti, Tania N.;Peters, Donna M.
本研究的目的是确定地塞米松 (DEX) 如何调节 αvβ3 整合素的表达和活性。 FACS 分析表明，DEX 处理诱导了活化的 αvβ3 整合素的表达。只要 DEX 存在，其表达就保持高水平，并在 DEX 去除后继续表达。 FACS分析表明αvβ3整合素的上调是β3整合素亚基表达增加的结果。通过实时 qPCR，与对照相比，DEX 治疗第 2 天诱导 β3 整合素 mRNA 增加 6.2 倍（p<0.04），并在治疗 6 天后保持升高状态，然后在去除 DEX 后又继续升高 10 天。 β3 整合素 mRNA 水平的增加仅需要 1 天的 DEX 处理即可在不使用 DEX 的情况下增加 4 天的水平。相反，DEX 不会改变 β1 整合素 mRNA 或蛋白质水平。 DEX 诱导的 β3 整合素 mRNA 上调部分是由于其半衰期从对照培养物中的 22.5 小时增加到 60.7 小时（p<0.05），并且可以被 RU486 和放线菌酮抑制，表明需要 DEX 诱导的激活因子从头合成蛋白质。钙调神经磷酸酶抑制剂环孢菌素 A (CsA) 和 FK506 抑制 DEX 诱导的 β3 整合素 mRNA 增加。总之，DEX 诱导的 β3 整合素增加是继发性糖皮质激素反应，导致 αvβ3 整合素表达延长，并通过钙调神经磷酸酶/NFAT 途径上调 β3 整合素亚基。
The purpose of this study was to determine how dexamethasone (DEX) regulates the expression and activity of αvβ3 integrin. FACS analysis showed that DEX treatment induced expression of an activated αvβ3 integrin. Its expression remained high as long as DEX was present and continued following DEX removal. FACS analysis showed that the upregulation of αvβ3 integrin was the result of an increase in the expression of the β3 integrin subunit. By real time qPCR, DEX treatment induced a 6.2-fold increase (p<0.04) in β3 integrin mRNA by day 2 compared to control and remained elevated for 6 days of treatment and then an additional 10 days once the DEX was removed. The increase in β3 integrin mRNA levels required only 1 day of DEX treatment to increase levels for 4 days in the absence of DEX. In contrast, DEX did not alter β1 integrin mRNA or protein levels. The DEX-induced upregulation of β3 integrin mRNA was partly due to an increase in its half-life to 60.7 h from 22.5 h in control cultures (p<0.05) and could be inhibited by RU486 and cycloheximide, suggesting that DEX-induced de novo protein synthesis of an activation factor was needed. The calcineurin inhibitors cyclosporin A (CsA) and FK506 inhibited the DEX induced increase in β3 integrin mRNA. In summary, the DEX-induced increase in β3 integrin is a secondary glucocorticoid response that results in prolonged expression of αvβ3 integrin and the upregulation of the β3 integrin subunit through the calcineurin/NFAT pathway.
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影响因子：
4.4
作者：
Filla MS;Schwinn MK;Sheibani N;Kaufman PL;Peters DM
通讯作者：
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影响因子：
3.4
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通讯作者：
ARMALY, MF
影响因子：
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