Institute for Regenerative Medicine at Scott and White Hospital, Texas A&M Health Sciences Center, Temple, Texas, United States of America.
PLoS One. 2010 Apr 20;5(4):e10237. doi: 10.1371/journal.pone.0010237.
The epithelial cell response to stress involves the transmission of signals between contiguous cells that can be visualized as a calcium wave. In some cell types, this wave is dependent on the release of extracellular trinucleotides from injured cells. In particular, extracellular ATP has been reported to be critical for the epithelial cell response to stress and has recently been shown to be upregulated in tumors in vivo.
METHODOLOGY/PRINCIPAL FINDINGS: Here, we identify stanniocalcin-1 (STC1), a secreted pleiotrophic protein, as a critical mediator of calcium wave propagation in monolayers of pulmonary (A549) and prostate (PC3) epithelial cells. Addition of STC1 enhanced and blocking STC1 decreased the distance traveled by an extracellular ATP-dependent calcium wave. The same effects were observed when calcium was stimulated by the addition of exogenous ATP. We uncover a positive feedback loop in which STC1 promotes the release of ATP from cells in vitro and in vivo.
CONCLUSIONS/SIGNIFICANCE: The results indicated that STC1 plays an important role in the early response to mechanical injury by epithelial cells by modulating signaling of extracellular ATP. This is the first report to describe STC1 as a modulator or purinergic receptor signaling.
上皮细胞对压力的反应涉及相邻细胞之间信号的传递，这种信号可以被可视化成钙波。在某些细胞类型中，这种波依赖于受损细胞释放细胞外三核苷酸。特别是，细胞外 ATP 被报道对上皮细胞对压力的反应至关重要，并且最近在体内肿瘤中被证明上调。
方法/主要发现：在这里，我们确定了分泌的多功能蛋白 stanniocalcin-1 (STC1) 作为肺（A549）和前列腺（PC3）上皮细胞单层中钙波传播的关键介质。添加 STC1 增强了细胞外 ATP 依赖性钙波的传播距离，而阻断 STC1 则减少了钙波的传播距离。当通过添加外源性 ATP 刺激钙时，观察到相同的效果。我们揭示了一个正反馈回路，其中 STC1 促进了细胞在体外和体内释放 ATP。
结论/意义：结果表明，STC1 通过调节细胞外 ATP 的信号转导，在上皮细胞对机械损伤的早期反应中发挥重要作用。这是首次报道 STC1 作为调节剂或嘌呤能受体信号转导的作用。
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