Multiple cellular responses to serotonin contribute to epithelial homeostasis.
Multiple cellular responses to serotonin contribute to epithelial homeostasis.
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DOI：
10.1371/journal.pone.0017028
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发表时间：
2011-02-24
期刊：
影响因子：
3.7
通讯作者：
Horseman ND
中科院分区：
文献类型：
--
作者：
Pai VP;Horseman ND
上皮内稳态结合了内部变化（上皮更新）的矛盾概念，使解剖现状的维持。上皮细胞分化和细胞损失（细胞脱落和凋亡）形成上皮更新的重要组成部分。尽管细胞损失的机制正在被揭示，但通过调节细胞损失来调节上皮更新的关键触发因素仍然不确定。5-羟色胺作为一种常见的自分泌旁分泌调节剂出现在包括乳腺在内的多个器官的上皮细胞中。在这里，我们解决血清素是否影响上皮营业额。具体而言，5-羟色胺在调节上皮细胞脱落、凋亡和屏障功能中的作用。使用在小鼠体内的研究和一个强大的模型分化的人乳腺导管上皮细胞（MCF 10A），我们表明，血清素诱导乳腺上皮细胞脱落和破坏紧密连接的可逆方式。然而，在持续暴露时，5-羟色胺诱导补充细胞群的凋亡，引起上皮细胞膜的不可逆变化。由5-羟色胺诱导的这些事件的交错性质缓慢地将上皮中的平衡从可逆转变为不可逆。这些发现对我们控制上皮再生的能力具有非常重要的意义，从而解决异常上皮更新的病理学，其范围从退行性疾病（例如;胰腺炎和胰腺炎）至增殖性疾病（例如;乳腺炎、导管扩张、胆管病和上皮癌）。
Epithelial homeostasis incorporates the paradoxical concept of internal change (epithelial turnover) enabling the maintenance of anatomical status quo. Epithelial cell differentiation and cell loss (cell shedding and apoptosis) form important components of epithelial turnover. Although the mechanisms of cell loss are being uncovered the crucial triggers that modulate epithelial turnover through regulation of cell loss remain undetermined. Serotonin is emerging as a common autocrine-paracine regulator in epithelia of multiple organs, including the breast. Here we address whether serotonin affects epithelial turnover. Specifically, serotonin's roles in regulating cell shedding, apoptosis and barrier function of the epithelium. Using in vivo studies in mouse and a robust model of differentiated human mammary duct epithelium (MCF10A), we show that serotonin induces mammary epithelial cell shedding and disrupts tight junctions in a reversible manner. However, upon sustained exposure, serotonin induces apoptosis in the replenishing cell population, causing irreversible changes to the epithelial membrane. The staggered nature of these events induced by serotonin slowly shifts the balance in the epithelium from reversible to irreversible. These finding have very important implications towards our ability to control epithelial regeneration and thus address pathologies of aberrant epithelial turnover, which range from degenerative disorders (e.g.; pancreatitis and thyrioditis) to proliferative disorders (e.g.; mastitis, ductal ectasia, cholangiopathies and epithelial cancers).
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