Angiotensin II regulates parathyroid hormone-related protein expression in cultured rat aortic smooth muscle cells through transcriptional and post-transcriptional mechanisms.
Angiotensin II regulates parathyroid hormone-related protein expression in cultured rat aortic smooth muscle cells through transcriptional and post-transcriptional mechanisms.
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DOI：
10.1016/s0021-9258(18)53952-1
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发表时间：
1993-01
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影响因子：
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通讯作者：
C. Pirola;Hai Mei Wang;A. Kamyar;Siaoxing Wu;Hiro Enomoto;Behrooz Sharifi;J. Forrester;Thomas L. Clemens;Thomas L. Clemens;James A. Fagin;James A. Fagin
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文献类型：
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作者：
C. Pirola;Hai Mei Wang;A. Kamyar;Siaoxing Wu;Hiro Enomoto;Behrooz Sharifi;J. Forrester;Thomas L. Clemens;Thomas L. Clemens;James A. Fagin;James A. Fagin
甲状旁腺素相关蛋白（PTHrP），一种肿瘤产物，负责恶性相关的高钙血症，也产生于许多正常组织，包括血管平滑肌细胞（SMC）。由于PTHrP具有血管舒张特性，我们推测其他血管活性药物可能控制SMC中PTHrP基因的表达。血管紧张素II对去血清SMC的PTHrP mRNA的诱导作用在2 h时显著，4-6 h达高峰（6-10倍）。血管紧张素II对PTHrP基因表达的影响被saralasin抑制，saralasin是一种血管紧张素II受体拮抗剂，并被放线菌素D和放线菌酮阻断，这表明需要基因转录和蛋白质合成。核径流分析显示PTHrP基因转录增加3倍后，血管紧张素II治疗1小时。血管紧张素II也延长PTHrP mRNA半衰期2-3倍。血管紧张素诱导的PTHrP mRNA部分依赖于环氧合酶产物和蛋白激酶C激活。其他血管收缩物质，包括5-羟色胺和缓激肽，也刺激PTHrP的表达，而血管扩张剂心房利钠肽没有。加入重组PTHrP-（1-141）显著抑制血管紧张素II诱导的SMC DNA合成。PTHrP的表达增加血管紧张素II通过转录和转录后机制。此外，PTHrP调节血管紧张素II对SMC增殖的作用。这表明PTHrP局部作用于SMC，可能对抗血管收缩剂如血管紧张素II的血管活性和/或生长促进作用。
Parathyroid hormone-related protein (PTHrP), a tumor product responsible for malignancy-associated hypercalcemia, is also produced in many normal tissues, including vascular smooth muscle cells (SMC). As PTHrP exhibits vasodilatory properties, we postulated that other vasoactive agents may control PTHrP gene expression in SMC. Addition of angiotensin II to serum-deprived SMC resulted in a marked induction of PTHrP mRNA by 2 h, with a peak (6-10-fold) at 4-6 h. Angiotensin II effects on PTHrP gene expression were inhibited by saralasin, an angiotensin II receptor antagonist, and blocked by actinomycin D and cycloheximide, suggesting a requirement for gene transcription and protein synthesis. Nuclear run-off assays revealed a 3-fold increase in PTHrP gene transcription 1 h after angiotensin II treatment. Angiotensin II also prolonged PTHrP mRNA half-life by 2-3-fold. Angiotensin-induced PTHrP mRNA is partially dependent on cyclooxygenase products and protein kinase C activation. Other vasoconstrictor substances, including serotonin and bradykinin, also stimulated PTHrP expression, whereas the vasodilator atrial natriuretic peptide did not. Addition of recombinant PTHrP-(1-141) significantly inhibited angiotensin II-induced SMC DNA synthesis. PTHrP expression is increased by angiotensin II through transcriptional and post-transcriptional mechanisms. In addition, PTHrP modulates the effect of angiotensin II on SMC proliferation. This suggests that PTHrP acts locally in SMC, possibly to oppose the vasoactive and/or growth-promoting effects of vasoconstrictor agents such as angiotensin II.