Activation of the JAK/STAT pathway in vascular smooth muscle by serotonin
Activation of the JAK/STAT pathway in vascular smooth muscle by serotonin
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DOI：
10.1152/ajpcell.00385.2004
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发表时间：
2005-04-01
影响因子：
5.5
通讯作者：
Marrero, MB
中科院分区：
文献类型：
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作者：
Banes, AKL;Shaw, SM;Marrero, MB
血清素（5-羟色胺，5-HT）是一种血管收缩剂和促分裂剂，其水平在糖尿病中升高。以往的研究表明，5-HT 2A，5-HT 2B和5-HT 1B受体存在于血管平滑肌细胞（VSMCs）。目前还没有关于VSMC中JAK/STAT通路的5-HT 2B和5-HT 1B受体激活以及糖尿病中5-HT信号传导的潜在改变的数据。因此，我们测试的假设，5-HT差异激活JAK/ STAT通路在正常（5 mM）和高（25 mM）葡萄糖的条件下，在VSMCs。用5-HT（10（-6）M）处理大鼠VSMC导致JAK 2、JAK 1和STAT 1的时间依赖性激活（类似于2倍），但不包括STAT 3（5分钟时达到最大值，30分钟时恢复到基线）。5-HT 2B受体激动剂BW 723 C86和5-HT 1B受体激动剂CGS 12066 A（10（-9）-10（-5）M，5分钟刺激）不激活JAK/ STAT通路。用5-HT 2A受体拮抗剂酮色林（10 nM）处理可抑制5-HT对JAK 2的激活。用酮色林治疗链脲佐菌素诱导的糖尿病大鼠（5 mg中心点/kg（-1）中心点/天（-1））可降低体内去内皮胸主动脉中JAK 2和STAT 1的活化，但不能降低STAT 3的活化。5-HT（10（-6）M）处理导致细胞增殖增加和DNA合成增加，这被JAK 2抑制剂AG 490抑制。进一步研究夹竹桃素，氯化二苯碘铵，过氧化氢酶，和病毒转染的超氧化物歧化酶在任何葡萄糖浓度的JAK/ STAT通路的激活5-HT没有影响。因此，我们得出结论，5-HT激活JAK 2，JAK 1，和STAT 1通过5-HT 2A受体在活性氧物种的非依赖性方式在正常和高糖条件下。
Serotonin (5-hydroxytryptamine, 5-HT) is a vasoconstrictor and mitogen whose levels are elevated in diabetes. Previous studies have shown the presence of 5-HT2A, 5-HT2B, and 5-HT1B receptors in vascular smooth muscle cells (VSMCs). There are currently no data regarding 5-HT2B and 5-HT1B receptor activation of the JAK/STAT pathway in VSMCs and resultant potential alterations in 5-HT signaling in diabetes. Therefore, we tested the hypothesis that 5-HT differentially activates the JAK/ STAT pathway in VSMCs under conditions of normal ( 5 mM) and high ( 25 mM) glucose. Treatment of rat VSMCs with 5-HT ( 10(-6) M) resulted in time-dependent activation ( similar to 2-fold) of JAK2, JAK1, and STAT1, but not STAT3 ( maximal at 5 min, returned to baseline by 30 min). The 5-HT2B receptor agonist BW723C86 and the 5-HT1B receptor agonist CGS12066A ( 10(-9) - 10(-5) M, 5-min stimulation) did not activate the JAK/ STAT pathway. Treatment with the 5-HT2A receptor antagonist ketanserin ( 10 nM) inhibited JAK2 activation by 5-HT. Treatment of streptozotocin-induced diabetic rats with ketanserin ( 5 mg center dot kg(-1) center dot day(-1)) reduced activation of JAK2 and STAT1 but not STAT3 in endothelium-denuded thoracic aorta in vivo. 5-HT ( 10(-6) M) treatment resulted in increased cell proliferation and increased DNA synthesis, which were inhibited by the JAK2 inhibitor AG490. Further studies with apocynin, diphenyleneiodonium chloride, catalase, and virally transfected superoxide dismutase had no effect at either glucose concentration on activation of the JAK/ STAT pathway by 5-HT. Therefore, we conclude that 5-HT activates JAK2, JAK1, and STAT1 via the 5-HT2A receptors in a reactive oxygen species-independent manner under both normal and high glucose conditions.