Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, P.R. China.
Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, P.R. China.
Int J Mol Med. 2015 Mar;35(3):784-90. doi: 10.3892/ijmm.2014.2054. Epub 2014 Dec 29.
Infection is a significant cause of preterm birth. Abnormal changes in intracellular calcium signals are the ultimate triggers of early uterine contractions that result in preterm birth. T‑type calcium channels play an important role in the pathogenesis of cancer, as well as endocrine and cardiovascular diseases. However, there are limited studies on their role in uterine contractions and parturition. In the present study, mouse uterine smooth muscle cells were isolated and treated with lipopolysaccharides (LPS) to mimic the microenvironment of uterine infection in vitro to investigate the role of T‑type calcium channels in the process of infection‑induced preterm birth. The results from quantitative polymerase chain reaction and western blot analysis showed that LPS significantly induced the expression of the Cav3.1 and Cav3.2 subtypes of T‑type calcium channels. Measurements of intracellular calcium concentration showed a significant increase in response to LPS. However, these effects can be reversed by T‑type calcium channel blockers. Western blot analysis further indicated that LPS induced the activation of the nuclear factor (NF)‑κB signaling pathway, and endothelin‑1 (ET‑1) was significantly upregulated, whereas NF‑κB inhibitors significantly inhibited the LPS‑induced upregulation of Cav3.1, Cav3.2 and ET‑1 expression. In addition, ET‑1 directly induced Cav3.1 and Cav3.2 expression, whereas ET‑1 antagonists inhibited the LPS‑induced upregulation of Cav3.1 and Cav3.2 expression. In conclusion, the present study demonstrates that infection triggers the upregulation of T‑type calcium channels and promotes calcium influx. This process relies on the activation of the NF‑κB/ET‑1 signaling pathway. The T‑type calcium channel is expected to become an effective target for the prevention of infection‑induced preterm birth.
感染是早产的一个重要原因。细胞内钙信号的异常变化是导致早产的早期子宫收缩的最终触发因素。T 型钙通道在癌症、内分泌和心血管疾病的发病机制中发挥着重要作用。然而，关于它们在子宫收缩和分娩中的作用的研究有限。本研究中，通过分离小鼠子宫平滑肌细胞并用脂多糖（LPS）处理来模拟子宫感染的体外微环境，以研究 T 型钙通道在感染诱导早产过程中的作用。定量聚合酶链反应和 Western blot 分析的结果表明，LPS 显著诱导 T 型钙通道 Cav3.1 和 Cav3.2 亚基的表达。细胞内钙浓度的测量显示对 LPS 有明显的响应增加。然而，这些效应可被 T 型钙通道阻滞剂逆转。Western blot 分析进一步表明，LPS 诱导核因子（NF）-κB 信号通路的激活，内皮素-1（ET-1）显著上调，而 NF-κB 抑制剂显著抑制 LPS 诱导的 Cav3.1、Cav3.2 和 ET-1 表达的上调。此外，ET-1 直接诱导 Cav3.1 和 Cav3.2 的表达，而 ET-1 拮抗剂抑制 LPS 诱导的 Cav3.1 和 Cav3.2 表达的上调。综上所述，本研究表明感染触发 T 型钙通道的上调并促进钙内流。这一过程依赖于 NF-κB/ET-1 信号通路的激活。T 型钙通道有望成为预防感染性早产的有效靶点。
