Basic Medical Research Centre, Medical College of Nantong University, Nantong, China.
Department of Biochemistry, Medical College of Nantong University, Nantong, China.
Sci Rep. 2019 Jul 1;9(1):9500. doi: 10.1038/s41598-019-45932-3.
Neuropeptide Y (NPY) is an abundant neuropeptide in the mammalian central and peripheral nervous systems. Transgenic mice overexpressing NPY in noradrenergic neurons have increased level of hepatic triglycerides, fatty acids and cholesterol, which contributed to the development of hepatosteatosis. However, the roles of NPY in the activation of hepatic stellate cells (HSCs) and the underlying mechanisms remain unclear. This study aimed to investigate the expression and secretion of NPY in human immortalized HSC LX-2 cells and the regulatory function of NPY on the fibrogenic response in LX-2 cells, to explore the potential association between NPY and LX-2 activation. The results showed an increase in the expression and secretion of NPY(1-36) in activated LX-2 cells. Both endogenous and exogenous NPY(1-36) induced the phosphorylation of mTOR, p70S6K, and 4EBP1 and promoted the fibrogenic response via NPY Y1 receptor subtype (NPY1R), as these responses were blocked by either an NPY1R antagonist (BIBP3226) or NPY1R knockdown. Moreover, NPY(1-36) serum levels were increased in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) and presented a positive relationship with MELD scores in LC patients. These findings suggest that immortalized HSCs LX-2 have the potential to produce NPY(1-36). High serum levels of NPY(1-36) is correlated with hepatic dysfunction in cirrhotic patients.
神经肽 Y（NPY）是哺乳动物中枢和外周神经系统中丰富的神经肽。在去甲肾上腺素能神经元中过表达 NPY 的转基因小鼠肝甘油三酯、脂肪酸和胆固醇水平升高，导致肝脂肪变性的发生。然而，NPY 在肝星状细胞（HSCs）激活中的作用及其潜在机制尚不清楚。本研究旨在研究 NPY 在人永生化 HSC LX-2 细胞中的表达和分泌，以及 NPY 对 LX-2 细胞纤维生成反应的调节作用，以探讨 NPY 与 LX-2 激活之间的潜在关联。结果表明，激活的 LX-2 细胞中 NPY（1-36）的表达和分泌增加。内源性和外源性 NPY（1-36）均可诱导 mTOR、p70S6K 和 4EBP1 的磷酸化，并通过 NPY Y1 受体亚型（NPY1R）促进纤维生成反应，这些反应可被 NPY1R 拮抗剂（BIBP3226）或 NPY1R 敲低所阻断。此外，肝硬化（LC）和肝细胞癌（HCC）患者血清 NPY（1-36）水平升高，且与 LC 患者 MELD 评分呈正相关。这些发现表明，永生化 HSCs LX-2 具有产生 NPY（1-36）的潜力。肝硬化患者血清中 NPY（1-36）水平升高与肝功能障碍相关。
