Pancreatic stellate cells (PSCs) are the main functional cells leading to pancreatic fibrosis. Nicotine is widely considered as an independent risk factor of pancreatic fibrosis, but the mechanism is still unclear. Our study was aimed to explore the effects of nicotine on human pancreatic stellate cells (hPSCs) and involved pathways. Primary human PSCs were cultured and treated with nicotine (0.1 μM and 1 μM). The proliferation, apoptosis, α-SMA expression, extracellular matrix metabolism and autophagy of hPSCs were detected by CCK-8 assay, flow cytometry, real-time PCR and Western blotting analysis. The α7nAChR-mediated JAK2/STAT3 signaling pathway was also examined, and an α7nAChR antagonist α-bungarotoxin (α-BTX) was used to perform inhibition experiments. The proliferation, α-SMA expression and autophagy of hPSCs were significantly promoted by 1 μM nicotine. Meanwhile, the apoptosis of hPSCs was significantly reduced. The extracellular matrix metabolism of hPSCs was also regulated by nicotine. Moreover, the α7nAChR-mediated JAK2/STAT3 signaling pathway was activated by nicotine, this pathway and effects of nicotine can be blocked by α-BTX. Our finding suggests that nicotine can promote activation of human pancreatic stellate cells (hPSCs) through inducing autophagy via α7nAChR-mediated JAK2/STAT3 signaling pathway, providing a new insight into the mechanisms by which nicotine affects pancreatic fibrosis.

中文翻译：

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尼古丁通过α7nAChR介导的JAK2/STAT3信号通路诱导自噬促进人胰腺星状细胞活化


胰腺星状细胞（PSC）是导致胰腺纤维化的主要功能细胞。尼古丁被广泛认为是胰腺纤维化的独立危险因素，但其机制仍不清楚。我们的研究旨在探讨尼古丁对人胰腺星状细胞（hPSC）的影响及其相关途径。培养原代人 PSC，并用尼古丁（0.1 μM 和 1 μM）处理。采用CCK-8法、流式细胞仪、实时荧光定量PCR和Western blotting检测hPSC的增殖、凋亡、α-SMA表达、细胞外基质代谢和自噬。还检查了α7nAChR介导的JAK2/STAT3信号通路，并使用α7nAChR拮抗剂α-银环蛇毒素（α-BTX）进行抑制实验。 1 μM尼古丁显着促进hPSC的增殖、α-SMA表达和自噬。同时，hPSCs的凋亡显着减少。 hPSC 的细胞外基质代谢也受到尼古丁的调节。此外，α7nAChR介导的JAK2/STAT3信号通路被尼古丁激活，该通路和尼古丁的作用可以被α-BTX阻断。我们的研究结果表明，尼古丁可以通过α7nAChR介导的JAK2/STAT3信号通路诱导自噬，促进人胰腺星状细胞（hPSC）的激活，为尼古丁影响胰腺纤维化的机制提供了新的见解。