1-磷酸鞘氨醇受体3在心血管系统中的作用

1-磷酸鞘氨醇受体是1-磷酸鞘氨醇在细胞内发挥作用的重要靶点,包括5种亚型,广泛存在于包括心血管系统在内的各系统。近年来,许多研究发现1-磷酸鞘氨醇受体3在血管舒张、血管屏障功能、缺血再灌注损伤和动脉粥样硬化等过程中具有重要的生物学作用。现就1-磷酸鞘氨醇受体3在心血管系统中的作用及其机制做一综述。     

鞘氨醇激酶在血管相关疾病中的保护作用及其机制研究进展

鞘氨醇激酶是调控机体鞘脂代谢的重要激酶之一,具有广泛的生物学作用。越来越多的研究表明,鞘氨醇激酶与临床多种血管疾病的发生发展密切相关。机体缺血或血管损伤时,鞘氨醇激酶可通过诱导血管新生、调节血管收缩以及改善血管内皮细胞应激耐受能力等多种方式避免血管内皮细胞的应激损伤,从而维持血管的完整性。鞘氨醇激酶对血管相关疾病的保护作用可通过鞘氨醇激酶/1-磷酸鞘氨醇-RAS/细胞外调节蛋白激酶及鞘氨醇激酶1/1-磷酸鞘氨醇/沉默信息调节因子1等多条信号通路实现。现根据已报道的文献,针对鞘氨醇激酶在血管相关疾病中的保护作用及其机制做一综述。     

S1P/S1PR2的心血管调节作用及其信号通路

<正>1-磷酸鞘氨醇(sphingosine 1-phosphate,S1P)是近年来发现的在心血管研究中具有重要生理功能的一种膜磷脂类代谢产物。S1P通过与细胞表面的受体即1-磷酸鞘氨醇受体(sphingosine-1-phosphate receptos,S1PRs)作用而发挥其广泛的生物学效应。S1PR是G蛋白耦联受体家族成员之一,包括S1PR1、S1PR2、S1PR3、S1PR4、S1PR5,这些受体主要与G蛋白α亚基耦联而发挥不同的生物学功能[1]。S1P对心     

S1P及其受体在心血管系统中的作用

磷脂类是细胞膜的重要组成成分之一,并且在细胞生命活动的信号转导过程中同样也发挥着非常重要的作用。1-磷酸鞘氨醇(S1P)是近年来发现的具有重要生理功能的另一种膜磷脂类分解和代谢产物。它既可作为一种细胞内第二信使发挥作用,又可通过作用于细胞表面特定的受体而发挥其重要的生物学功能,包括细胞的增殖、存活、细胞骨架改变、迁移、血管发生、创伤愈合及在心血管系统、免疫系统方面都有着重要的作用〔1～5〕。本文综述S1P在心血管系统中的生理病理作用。     

1-磷酸鞘氨醇与支气管哮喘

1-磷酸鞘氨醇是一类生物活性鞘脂类代谢物,不仅可以作为第一信使与G蛋白耦联受体结合,也可以作为第二信使参与调节细胞的发育、增殖、重塑、生存和活化细胞等生物效应。近些年的研究证实,1-磷酸鞘氨醇及其信号通路对于支气管哮喘的发生、发展起到了非常重要的作用。这将或许为支气管哮喘的治疗提供一个新途径,本文主要就1-磷酸鞘氨醇与支气管哮喘的关系作一综述。     

1-磷酸鞘氨醇与支气管哮喘

1-磷酸鞘氨醇是一类生物活性鞘脂类代谢物,不仅可以作为第一信使与G蛋白耦联受体结合,也可以作为第二信使参与调节细胞的发育、增殖、重塑、生存和活化细胞等生物效应.近些年的研究证实,1-磷酸鞘氨醇及其信号通路对于支气管哮喘的发生、发展起到了非常重要的作用.这将或许为支气管哮喘的治疗提供一个新途径,本文主要就1-磷酸鞘氨醇与支气管哮喘的关系作一综述.     

1-磷酸神经鞘氨醇对心血管系统的作用

1-磷酸神经鞘氨醇(S1P)是一种有生物活性的脂质代谢产物,具有调节细胞增殖、再生、迁移及细胞内钙离子移动、黏附分子表达和激活单核细胞黏附内皮细胞等生物功效,在血管生理性再生及动脉粥样硬化斑块发生发展中起着重要作用。本文综述S1P在心血管系统中的生理病理作用。     

高密度脂蛋白结合1-磷酸鞘氨醇的血管保护作用研究进展

血液高密度脂蛋白中的1-磷酸鞘氨醇参与了血管扩张、血管再生、内皮屏障及抗动脉粥样硬化形成等高密度脂蛋白的多种功能。现对高密度脂蛋白结合1-磷酸鞘氨醇的血管保护功能做一综述。     

鞘氨醇激酶信号通路在肝纤维化中的作用机制

肝纤维化的形成主要体现为肝星状细胞的激活和细胞外基质合成降解的失衡。鞘氨醇激酶-1-磷酸鞘氨醇-1-磷酸鞘氨醇受体(SphK-S1P-S1PRs)信号通路在调控细胞的增殖、迁移以及炎症反应等生命活动中发挥重要作用。介绍了SphK、S1P、S1PRs的分布及生物学功能,简述了SphK-S1P-S1PRs信号通路在肝纤维化中的作用机制及其研究进展。多项研究证实SphK-S1P-S1PRs信号通路在肝纤维化疾病研究中起关键性作用,深入的探索有助于为临床上肝纤维化治理和药物新靶点开发提供新的思路。     

1-磷酸鞘氨醇在心血管疾病中的研究进展

<正>1-磷酸鞘氨醇(sphingosine-1-phosphate,S1P)是一种多效性的脂质,具有广泛的生理和病理生理作用~([1-2])。人们对S1P的研究已有近三十年。已有研究表明S1P参与多种生理、病理生理过程,包括血管生成、细胞的增殖和迁移,炎症细胞的运输,细胞因子的产生、细胞骨架重组、内皮屏障调节血管张力控制等。现就S1P在心血管系统中作用的研究进展进行综述。     

Unveiling the biological role of sphingosine-1-phosphate receptor modulators in inflammatory bowel diseases

Inflammatory bowel disease(IBD) is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide. The increasing disease burden worldwide, lack of response to current biologic therapeutics, and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy. Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effec...     

Lysophospholipids enhance matrix metalloproteinase-2 expression in human endothelial cells

Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both low-molecular-weight lysophospholipids, which promote cell proliferation, migration, and invasion via interaction with a family of specific G protein-coupled receptors. Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes, which are involved in degradation of the extracellular matrix and play critical roles in endothelial cell migration and matrix remodeling during angiogenesis. Among these MMPs, MMP-2 is known to trigger cell migration. In our present study, we examined the effects of LPA and S1P on MMP-2 expression in human endothelial cells. We showed that LPA and S1P enhanced MMP-2 expression in mRNA, protein levels, and also enzymatic activity of cells of the EAhy926 human endothelial cell line. The enhancement effects occurred in concentration- and time-dependent manners. Results from real-time PCR, Western blots, and substrate gels indicated that these enhancement effects were mediated through MAPK kinase/ERK-, nuclear factor-kappaB-, and calcium influx-dependent pathways. Furthermore, we show that endothelial cell invasion of the gel was enhanced by lysophospholipids, and the induction could be prevented by an MMP inhibitor, GM6001. These observations suggest that LPA and S1P may play important roles in endothelial cell invasion by regulating the expression of MMP-2.     

Pro-phagocytic Effects of Thymoquinone on Cigarette Smoke-exposed Macrophages Occur by Modulation of the Sphingosine-1-phosphate Signalling System

Oxidative stress, inflammation, increased bronchial epithelial cell apoptosis, and deficient phagocytic clearance of these cells (efferocytosis) by the alveolar macrophages are present in chronic obstructive pulmonary disease (COPD) and in response to cigarette smoke. We previously showed that the macrophage dysfunction is associated with changes to the sphingosine-1-phosphate (S1P) signalling system. We hypothesized that the antioxidant/anti-inflammatory agent, thymoquinone, would improve macrophage phagocytosis via modulation of the S1P system and protect bronchial epithelial cells from cigarette smoke or lipopolysaccharide (LPS)-induced apoptosis. Phagocytosis was assessed using flow cytometry, S1P mediators by Real-Time PCR, and apoptosis of 16HBE bronchial epithelial cells using flow cytometry and immunohistochemistry. Cigarette smoke and LPS decreased phagocytosis and increased S1P receptor (S1PR)-5 mRNA in THP-1 macrophages. Thymoquinone enhanced efferocytic/phagocytic ability, antagonized the effects of cigarette smoke extract and LPS on phagocytosis and S1PR5, and protected bronchial epithelial cells from cigarette smoke-induced apoptosis. Thymoquinone is worth further investigating as a potential therapeutic strategy for smoking-related lung diseases.     

Sphingosine-1-Phosphate Signaling in Endothelial Disorders

Numerous preclinical studies indicate that sustained endothelial activation significantly contributes to tissue edema, perpetuates the inflammatory response, and exacerbates tissue injury ultimately resulting in organ failure. However, no specific therapies aimed at restoring endothelial function are available as yet. Sphingosine-1-phosphate (S1P) is emerging as a potent modulator of endothelial function and endothelial responses to injury. Recent studies indicate that S1PR are attractive targets to treat not only disorders of the arterial endothelium but also microvascular dysfunction caused by ischemic or inflammatory injury. In this article, we will review the current knowledge of the role of S1P and its receptors in endothelial function in health and disease, and we will discuss the therapeutic potential of targeting S1PR not only for disorders of the arterial endothelium but also the microvasculature. The therapeutic targeting of S1PR in the endothelium could help to bridge the gap between biomedical research in vascular biology and clinical practice.     

模拟失重大鼠胸主动脉和腹主动脉S1P/S1PRs通路改变

目的 研究四周模拟失重对大鼠胸主动脉(TA)和腹主动脉（AA）1-磷酸鞘氨醇（S1P）及其受体（S1PRs）蛋白表达和分布的影响。 方法 SD大鼠28只，随机分为对照（CON）组和悬吊（HU）组，每组14只（n=14）。采用尾部悬吊建立大鼠模拟失重模型，时间为4周。苏木精-伊红（HE）染色观察动脉的结构变化，Western blot和免疫组织化学染色检测神经鞘氨醇激酶（SphK）1和（SphK）2、S1P裂解酶（SGPL）1、1-3型S1PRs（S1PR1、S1PR2、S1PR3）、增殖细胞核抗原（PCNA）和I型胶原蛋白（COL1）的蛋白表达和分布变化。 结果 悬吊4周后，与CON组相比，HU组TA的SphK1表达无明显改变，而SphK2和SGPL1表达降低（P<0.05），S1PRs表达和分布均无明显改变；同时，与CON组相比，HU组大鼠TA内-中膜厚度（IMT）和横截面积(CSA)增加，PCNA表达显著增加（P<0.05），但COL1表达无明显变化。与TA不同，与CON组比较，四周尾部悬吊后AA的SphK1、SphK2与SGPL1表达显著增加（P<0.05），S1PR1和S1PR3表达显著降低（P<0.05），IMT、CSA和PCNA表达无显著变化，但COL1表达显著减少（P<0.05）。此外，CON组AA的SphK1、SphK2、SGPL1、S1PR3、PCNA和COL1的蛋白表达均显著低于TA（P<0.05），S1PR1蛋白表达则高于TA（P<0.05），IMT与CSA均小于TA（P<0.05）。 结论 模拟失重大鼠TA与AA的S1P合成和降解过程发生部位特异性改变，可能与其平滑肌细胞增殖程度有关；S1P及其受体含量在TA和AA间存在部位差异。      

寄生虫病中神经酰胺信号通路的研究进展

神经酰胺和鞘胺醇-1-磷酸是具有生物活性的鞘磷脂,它们不仅是构成细胞膜的重要组分,也可以作为第二信使在细胞信号转导中发挥重要的作用.神经酰胺具有诱导细胞凋亡、自噬及促进炎症反应等作用,而鞘胺醇-1-磷酸具有促进细胞生长、增殖、分化及诱导免疫细胞迁移等作用.由神经酰胺、鞘胺醇-1-磷酸及关键酶构成的神经酰胺信号通路参与癌...     

Role of the lysophospholipid mediators lysophosphatidic acid and sphingosine 1-phosphate in lung fibrosis

Aberrant wound healing responses to lung injury are believed to contribute to fibrotic lung diseases, such as idiopathic pulmonary fibrosis (IPF). The lysophospholipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), by virtue of their ability to mediate many basic cellular functions, including survival, proliferation, migration, and contraction, can influence many of the biological processes involved in wound healing. Accordingly, recent investigations indicate that LPA and S1P may play critical roles in regulating the development of lung fibrosis. Here we review the evidence indicating that LPA and S1P regulate pulmonary fibrosis and the potential mechanisms through which these lysophospholipids may influence fibrogenesis induced by lung injury.     

MicroRNA-21 in Cardiovascular Disease

MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular disease conditions such as proliferative vascular disease, cardiac hypertrophy and heart failure, and ischemic heart disease. miR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Accordingly, miR-21 is proven to be involved in the pathogenesis of the above-mentioned cardiovascular diseases as demonstrated by both loss-of-function and gain-of-function approaches. Programmed cell death 4 (PDCD4), phosphatase and tensin homology deleted from chromosome 10 (PTEN), sprouty1 (SPRY1), and sprouty2 (SPRY2) are the current identified target genes of miR-21 that are involved in miR-21-mediated cardiovascular effects. miR-21 might be a novel therapeutic target in cardiovascular diseases. This review article summarizes the research progress regarding the roles of miR-21 in cardiovascular disease.