Evidence from a novel human cell clone that adult vascular smooth muscle cells can convert reversibly between noncontractile and contractile phenotypes
Evidence from a novel human cell clone that adult vascular smooth muscle cells can convert reversibly between noncontractile and contractile phenotypes
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DOI：
10.1161/01.res.85.4.338
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发表时间：
1999-08-20
影响因子：
20.1
通讯作者：
Pickering, JG
中科院分区：
文献类型：
--
作者：
Li, SH;Sims, S;Pickering, JG
平滑肌细胞 (SMC) 执行多种功能，可分为收缩细胞和合成细胞。传统模型认为，这些不同的功能是由同一细胞凭借其双向调节表型的能力来执行的。然而，这一模型受到了挑战，部分原因是没有生理学证据表明成体合成 SMC 可以获得收缩能力。我们通过从人胸廓内动脉克隆成人 SMC 来寻找证据。一种克隆，HITB5，表达平滑肌α-肌动蛋白、平滑肌球蛋白重链、重钙结合蛋白和钙调蛋白，并在组胺和血管紧张素 II 的反应中表现出强烈的钙瞬变，这证实了完整的跨膜信号级联。血清撤除后，这些细胞呈现拉长的纺锤形形态，随机迁移减慢，细胞外基质蛋白产量下降，细胞增殖和[H-3]胸苷掺入下降至接近0。然而，细胞活力并未受到损害；事实上，细胞凋亡率显着下降。在这种状态下，激动剂诱导的细胞质钙的升高甚至更加明显，并且伴随着 SMC 收缩。 10%血清的再添加使HITB5细胞完全恢复至非收缩、增殖表型。血清停药后收缩蛋白表达增加，尽管幅度不大，这表明向收缩功能的转变涉及现有收缩结构的重组或敏化。据我们所知，HITB5 SMC 的生理特性首次直接证明了培养的人类成人 SMC 可以在合成的非收缩状态和收缩状态之间转换。 HITB5 细胞对于表征这一关键转变的基础应该很有价值。
Smooth muscle cells (SMCs) perform diverse functions that can be categorized as contractile and synthetic. A traditional model holds that these distinct functions are performed by the same cell, by virtue of its capacity for bidirectional modulation of phenotype. However, this model has been challenged, in part because there is no physiological evidence that an adult synthetic SMC can acquire the ability to contract. We sought evidence for this by cloning adult SMCs from human internal thoracic artery. One clone, HITB5, expressed smooth muscle alpha-actin, smooth myosin heavy chains, heavy caldesmon, and calponin and showed robust calcium transients in response to histamine and angiotensin II, which confirmed intact transmembrane signaling cascades. On serum withdrawal, these cells adopted an elongated and spindle-shaped morphology, random migration slowed, extracellular matrix protein production fell, and cell proliferation and [H-3]thymidine incorporation fell to near 0. Cell viability was not compromised, however; in fact, apoptosis rate fell significantly. In this state, agonist-induced elevation of cytoplasmic calcium was even more: pronounced and was accompanied by SMC contraction. Readdition of 10% serum completely-returned HITB5 cells to a noncontractile, proliferative phenotype. contractile protein expression increased after serum withdrawal, although modestly, which suggested that the switch to contractile function involved reorganization or sensitization of existing contractile structures. To our knowledge, the physiological properties of HITB5 SMCs provide the first direct demonstration that cultured human adult SMCs can convert between a synthetic, noncontracting state and a contracting state. HITB5 cells should be valuable for characterizing the basis of this critical transition.