Intercellular calcium waves mediate preferential cell growth toward the wound edge in polarized hepatic cells

Intercellular calcium waves mediate preferential cell growth toward the wound edge in polarized hepatic cells
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DOI:
10.1016/s0014-4827(03)00160-5
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发表时间:
2003-07-15
影响因子:
3.7
通讯作者:
Lin, CH
Lin, CH
中科院分区:
医学3区
文献类型:
--
作者:
Sung, YJ;Sung, ZL;Lin, CH

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在肝脏再生过程中,肝细胞感知损伤并通过尚不清楚的机制启动静止细胞的增殖。在这里,我们用培养的肝细胞来研究细胞间钙在介导伤口愈合过程中所起的作用。分化良好和极化的Hep-G2细胞通过诱导细胞分裂修复实验诱导的伤口。由此产生的细胞生长并没有均匀地发生在愈合细胞草坪上;相反,在距离伤口边缘150-200米的范围内,细胞增殖的活跃程度是其他地方的三倍;在低分化和/或非极化细胞中没有观察到这种绕周优先细胞生长。我们提供的实验证据表明,损伤过程本身可以引起钙波的传播,有趣的是,阻断这种与损伤相关的细胞间钙通信可以有效地抑制沿伤口边缘的偏向细胞生长。基于光刻的模式细胞培养系统被用来帮助描述这种类型的钙信号传导的机制。总之,我们的研究结果表明,在肝组织损失的情况下,通过传播钙波的细胞间通信协调再生细胞增殖。(C) 2003 Elsevier Science(美国)版权所有。
During liver regeneration, hepatocytes sense the damage and initiate proliferation of the quiescent cells through poorly understood mechanisms. Here, we have used cultured hepatic cells to study the roles played by intercellular calcium in mediating wound-healing processes. Well-differentiated and polarized Hep-G2 cells repaired an experimentally induced wound by induction of cell divisions. The resulting cellular growth did not occur evenly across the healing cell lawn; instead, proliferations were three times more active within 150-200 mum from the wound edge than further away; this periwound preferential cell growth was not observed in the poorly differentiated and/or nonpolarized cells. We have provided experimental evidence demonstrating that the wounding procedure itself could elicit a propagating calcium wave, and interestingly, blocking this injury-associated intercellular calcium communication could effectively inhibit the biased cell growth along the margin of the wound. A photolithography-based patterned cell culture system was employed to help delineate the mechanisms underlying this type of calcium signaling. In conclusion, our results suggested that intercellular communications via propagating calcium waves coordinate regenerative cell proliferations in response to hepatic tissue losses. (C) 2003 Elsevier Science (USA). All rights reserved.