Neuropilins(NRPs) are highly conserved transmembrane glycoproteins that possess pleiotropic functions. Neuropilin-1(NRP1) and its homologue neuropilin-2 interact as coreceptors with both class 3 semaphorins and vascul...Neuropilins(NRPs) are highly conserved transmembrane glycoproteins that possess pleiotropic functions. Neuropilin-1(NRP1) and its homologue neuropilin-2 interact as coreceptors with both class 3 semaphorins and vascular endothelial growth factor and are involved in neuronal guidance and angiogenesis, respectively. The contribution of NRPs to tumor angiogenesis has been highlighted in previous studies, leading to the development of NRP antagonists as novel anti-angiogenesis therapies. However, more recent studies have demonstrated that NRPs have a much broader spectrum of activity in the integration of different pathways in physiological and pathological conditions. A few studies investigated the role of NRPs in both malignant and non-neoplastic liver diseases. In normal liver, NRP1 is expressed in hepatic stellate cells and liver sinusoidal endothelial cells. NRP1 expression in hepatocytes has been associated with malignant transformation and may play an important role in tumor behavior. A contribution of NRPs in sinusoidal remodeling during liver regeneration has been also noted. Studies in chronic liver diseases have indicated that, besides its influence on angiogenesis, NRP1 might contribute to the progression of liver fibrosis owing to its effects on other growth factors, including transforming growth factor β1. As a result, NRP1 has been identified as a promising therapeutic target for future antifibrotic therapies based on the simultaneous blockade of multiple growth factor signaling pathways. In this review, the structure of NRPs and their interactions with various ligands and associated cell surface receptors are described briefly. The current understanding of the roles of the NRPs in liver diseases including tumors, regeneration and fibrogenesis, are also summarized.展开更多
目的:应用蛋白芯片技术筛选并探讨参苈加颗粒对心力衰竭大鼠心肌Neuropilin-2表达的影响。方法:将70只清洁级雄性Wi st ar大鼠随机抽取空白组15只,其余用阿霉素造模,将造模成功大鼠随机分为模型组和治疗组,分别给予参苈加颗粒和生理盐...目的:应用蛋白芯片技术筛选并探讨参苈加颗粒对心力衰竭大鼠心肌Neuropilin-2表达的影响。方法:将70只清洁级雄性Wi st ar大鼠随机抽取空白组15只,其余用阿霉素造模,将造模成功大鼠随机分为模型组和治疗组,分别给予参苈加颗粒和生理盐水灌胃每日1次,28天后取大鼠左心室组织,用于HE染色和蛋白芯片分析。结果:HE染色显示空白组大鼠心肌正常;模型组大鼠心肌纤维增粗、紊乱,间质增生,少量炎症细胞浸润;治疗组大鼠心肌排列较整齐,间质无明显增生,未见炎症细胞浸润。蛋白芯片可见Neuropilin-2存在差异性表达,与空白组相比,Neuropilin-2在模型组的表达下调;与模型组比较,Neuropilin-2在参苈加治疗组的表达上调;其余2组比较无表达差异。结论:参苈加颗粒可通过调节心肌Neuropilin-2的表达改善心肌纤维化和心肌细胞凋亡,对慢性心衰大鼠心脏起保护作用。展开更多
文摘Neuropilins(NRPs) are highly conserved transmembrane glycoproteins that possess pleiotropic functions. Neuropilin-1(NRP1) and its homologue neuropilin-2 interact as coreceptors with both class 3 semaphorins and vascular endothelial growth factor and are involved in neuronal guidance and angiogenesis, respectively. The contribution of NRPs to tumor angiogenesis has been highlighted in previous studies, leading to the development of NRP antagonists as novel anti-angiogenesis therapies. However, more recent studies have demonstrated that NRPs have a much broader spectrum of activity in the integration of different pathways in physiological and pathological conditions. A few studies investigated the role of NRPs in both malignant and non-neoplastic liver diseases. In normal liver, NRP1 is expressed in hepatic stellate cells and liver sinusoidal endothelial cells. NRP1 expression in hepatocytes has been associated with malignant transformation and may play an important role in tumor behavior. A contribution of NRPs in sinusoidal remodeling during liver regeneration has been also noted. Studies in chronic liver diseases have indicated that, besides its influence on angiogenesis, NRP1 might contribute to the progression of liver fibrosis owing to its effects on other growth factors, including transforming growth factor β1. As a result, NRP1 has been identified as a promising therapeutic target for future antifibrotic therapies based on the simultaneous blockade of multiple growth factor signaling pathways. In this review, the structure of NRPs and their interactions with various ligands and associated cell surface receptors are described briefly. The current understanding of the roles of the NRPs in liver diseases including tumors, regeneration and fibrogenesis, are also summarized.
文摘目的:应用蛋白芯片技术筛选并探讨参苈加颗粒对心力衰竭大鼠心肌Neuropilin-2表达的影响。方法:将70只清洁级雄性Wi st ar大鼠随机抽取空白组15只,其余用阿霉素造模,将造模成功大鼠随机分为模型组和治疗组,分别给予参苈加颗粒和生理盐水灌胃每日1次,28天后取大鼠左心室组织,用于HE染色和蛋白芯片分析。结果:HE染色显示空白组大鼠心肌正常;模型组大鼠心肌纤维增粗、紊乱,间质增生,少量炎症细胞浸润;治疗组大鼠心肌排列较整齐,间质无明显增生,未见炎症细胞浸润。蛋白芯片可见Neuropilin-2存在差异性表达,与空白组相比,Neuropilin-2在模型组的表达下调;与模型组比较,Neuropilin-2在参苈加治疗组的表达上调;其余2组比较无表达差异。结论:参苈加颗粒可通过调节心肌Neuropilin-2的表达改善心肌纤维化和心肌细胞凋亡,对慢性心衰大鼠心脏起保护作用。
