ENDOTHELIN-1 STIMULATES DNA-SYNTHESIS AND PROLIFERATION OF PULMONARY-ARTERY SMOOTH-MUSCLE CELLS
ENDOTHELIN-1 STIMULATES DNA-SYNTHESIS AND PROLIFERATION OF PULMONARY-ARTERY SMOOTH-MUSCLE CELLS
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DOI：
10.1152/ajpcell.1992.263.6.c1295
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发表时间：
1992-12-01
影响因子：
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通讯作者：
MALIK, AB
中科院分区：
文献类型：
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作者：
JANAKIDEVI, K;FISHER, MA;MALIK, AB
内皮素-1（ET-1）是一种由内皮细胞释放的21个氨基酸组成的多肽，具有多种生物学效应，包括血管平滑肌细胞（VSMC）收缩、次级介质释放和细胞增殖。本研究旨在探讨ET-1对体外培养的肺动脉VSMC的增殖作用。在低血清和低表皮生长因子（EGF）存在下，ET-1刺激VSMC DNA合成和增殖。血清中的促成因子似乎是血小板衍生生长因子（PDGF），因为PDGF的抗体消除了刺激活性。EGF的抗体也阻止了刺激，这表明PDGF和EGF都是ET-1的VSMC生长促进活性的充分表达所必需的。ET-1对VSMC作用的一个矛盾方面是，当两种因子加在一起达到高基线DNA合成活性时，ET-1抑制EGF刺激的DNA合成的能力。如果在加入EGF后12-18 h加入ET-1或将ET-1和EGF加入到蛋白激酶C缺失的VSMC中，则抑制被阻止。ET-1的抑制作用可能是通过激活蛋白激酶C，然后抑制EGF与其受体的结合而介导的。结果表明，ET-1在适当条件下对肺动脉VSMC的生长有正、负两方面的调节作用。
Endothelin-1 (ET-1), a 21-amino acid peptide released from the endothelium, elicits a variety of biological effects that include vascular smooth muscle cell (VSMC) contraction, release of secondary mediators, and cell proliferation. The present study was undertaken to examine the proliferative potential of ET-1 toward pulmonary artery VSMC in culture. In the presence of low serum and epidermal growth factor (EGF), ET-1 stimulated marked DNA synthesis and proliferation of VSMC. The contributing factor from serum appeared to be platelet-derived growth factor (PDGF) because the antibody to PDGF eliminated the stimulatory activity. The antibody to EGF also prevented the stimulation, suggesting that both PDGF and EGF are required for the full expression of the VSMC growth-promoting activity of ET-1. A paradoxical aspect of ET-1 effect on VSMC was the ability of ET-1 to inhibit the EGF-stimulated DNA synthesis when the two factors were added together to a high baseline DNA synthetic activity. The inhibition was prevented if ET-1 was added 12-18 h after the addition of EGF or if ET-1 and EGF were added to a protein kinase C-depleted VSMC. The inhibition by ET-1 may be mediated by protein kinase C activation followed by inhibition of EGF binding to its receptor. The results indicate that ET-1 under appropriate conditions can modulate the growth of pulmonary artery VSMC in both positive and negative directions.