Serum can overcome contact inhibition in confluent human pulmonary artery smooth muscle cells.
Serum can overcome contact inhibition in confluent human pulmonary artery smooth muscle cells.
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DOI：
10.1371/journal.pone.0071490
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fouty BW
中科院分区：
文献类型：
--
作者：
Solodushko V;Khader HA;Fouty BW
完整血管中的肺动脉内皮细胞（PAEC）持续暴露于血清中，但除非受到损伤，否则不会增殖，受到汇合的限制。相比之下，肺动脉平滑肌细胞（PASMC）达到，并保持，融合在最低血清的存在下，保护血清的刺激作用，除非当内皮屏障变得更具渗透性。因此，我们假设，在血清存在下，汇合的PASMC可能比PAEC更少受到接触抑制的限制，并通过将汇合的非转化的人PAEC和PASMC暴露于含有增加浓度的胎牛血清（FBS）的培养基中并测定7天内的细胞生长来测试这一想法。在低血清中达到汇合的PAEC即使暴露于5%血清（最高检测浓度）也不增殖。相比之下，在低血清中达到汇合的PASMC在血清水平升高后确实增殖，这种效应具有剂量依赖性。与这一观察结果一致，与0.2%FBS相比，PASMC具有更多的BrdU掺入和更大的S期细胞百分比，而在PAEC中没有观察到这种差异。这些结果表明，汇合的人PAEC对血清的刺激作用有抗性，而汇合的PASMC在血清水平增加时可以增殖，这种作用部分由磷酸肌醇3-激酶活化的差异介导。该观察结果可能与理解在患有肺动脉高压的人类和动物中观察到的PASMC增生有关，其中由于缺氧或损伤导致的内皮通透性变化使底层平滑肌暴露于血清。
Pulmonary artery endothelial cells (PAEC) in an intact vessel are continually exposed to serum, but unless injured, do not proliferate, constrained by confluence. In contrast, pulmonary artery smooth muscle cells (PASMC) attain, and maintain, confluence in the presence of minimal serum, protected from serum’s stimulatory effects except when the endothelial barrier becomes more permeable. We hypothesized therefore, that confluent PASMC may be less constrained by contact inhibition in the presence of serum than PAEC and tested this idea by exposing confluent non-transformed human PAEC and PASMC to media containing increasing concentrations of fetal bovine serum (FBS) and determining cell growth over 7 days. PAEC that had attained confluence in low serum did not proliferate even when exposed to 5% serum, the highest concentration tested. In contrast, PASMC that attained confluence in low serum did proliferate once serum levels were increased, an effect that was dose dependent. Consistent with this observation, PASMC had more BrdU incorporation and a greater percentage of cells in S phase in 5% compared to 0.2% FBS, whereas no such difference was seen in PAEC. These results suggest that confluent human PAEC are resistant to the stimulatory effects of serum, whereas confluent PASMC can proliferate when serum levels are increased, an effect mediated in part by differences in phosphoinositide 3-kinase activation. This observation may be relevant to understanding the PASMC hyperplasia observed in humans and animals with pulmonary hypertension in which changes in endothelial permeability due to hypoxia or injury expose the underlying smooth muscle to serum.
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影响因子：
4.8
作者：
Burkart, A;Samii, B;Shpetner, HS
通讯作者：
Shpetner, HS
影响因子：
8
作者：
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Rothblum, LI
影响因子：
4.3
作者：
Azar, Rania;Susini, Christiane;Pyronnet, Stephane
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Pyronnet, Stephane
影响因子：
15.9
作者：
Lai, KH;Wang, H;Haber, E
通讯作者：
Haber, E
DOI：
10.1152/ajplung.1999.277.2.l282
发表时间：
1999-08-01
影响因子：
4.9
作者：
Lee, SL;Wang, WW;Fanburg, BL
通讯作者：
Fanburg, BL