AIM: To examine the expression of SphK1, an oncogenic kinase that produces sphingosine 1-phosphate (S1P), and its correlation with the expression of LPAR2, a major lysophosphatidic acid (LPA) receptor overexpressed in...AIM: To examine the expression of SphK1, an oncogenic kinase that produces sphingosine 1-phosphate (S1P), and its correlation with the expression of LPAR2, a major lysophosphatidic acid (LPA) receptor overexpressed in various cancers, in human colorectal cancer.METHODS: Real-time reverse-transcription polymerase chain reaction was used to measure the mRNA expression of SphK1, LPAR2, and the three major S1P receptors in 27 colorectal cancer samples and corresponding normal tissue samples. We also examined the correlation between the expression of SphK1 and LPAR2.RESULTS: Colorectal cancer tissue in 22 of 27 patients had higher levels of SphK1 mRNA than in normal tissue. In two-thirds of the samples, SphK1 mRNA expression was more than two-fold higher than in normal tissue. Consistent with previous reports, LPAR2 mRNA expression in 20 of 27 colorectal cancer tissue samples was higher compared to normal tissue samples. Expression profiles of all three major S1P receptors, S1PR1, S1PR2, and S1PR3, varied without any trend, with no significant difference in expression between cancer and normal tissues. A highly significant positive correlation was found between SphK1 and LPAR2 expression [Pearson’s correlation coefficient (r) = 0.784 and P < 0.01]. The mRNA levels of SphK1 and LPAR2 did not correlate with TNM stage.CONCLUSION: Our findings suggest that S1P and LPA may play important roles in the development of colorectal cancer via the upregulation of SphK1 and LPAR2, both of which could serve as new therapeutic targets in the treatment of colorectal cancer.展开更多
Lysophosphatidic acid(LPA), a glycerophospholipid, consists of a glycerol backbone connected to a phosphate head group and an acyl chain linked to sn-1 or sn-2 position. In the circulation, LPA is in submillimolar ran...Lysophosphatidic acid(LPA), a glycerophospholipid, consists of a glycerol backbone connected to a phosphate head group and an acyl chain linked to sn-1 or sn-2 position. In the circulation, LPA is in submillimolar range and mainly derived from hydrolysis of lysophosphatidylcholine, a process mediated by lysophospholipase D activity in proteins such as autotaxin(ATX). Intracellular and extracellular LPAs act as bioactive lipid mediators with diverse functions in almost every mammalian cell type. The binding of LPA to its receptors LPA1-6 activates multiple cellular processes such as migration, proliferation and survival. The production of LPA and activation of LPA receptor signaling pathways in the events of physiology and pathophysiology have attracted the interest of researchers. Results from studies using transgenic and gene knockout animals with alterations of ATX and LPA receptors genes, have revealed the roles of LPA signaling pathways in metabolic active tissues and organs. The present review was aimed to summarize recent progresses in the studies of extracellular and intracellular LPA production pathways. This includes the functional, structural and biochemical properties of ATX and LPA receptors. The potential roles of LPA production and LPA receptor signaling pathways in obesity, insulin resistance and liver fibrosis are also discussed.展开更多
目的探讨溶血磷脂酸(lysophosphatidic acid,LPA)对人肺成纤维细胞(HFL-1)白细胞介素-13受体α2(IL-13Rα2)表达和Ⅰ型胶原(collagen typeⅠ,COLAⅠ)合成的影响。方法细胞培养,显微镜观察LPA对HFL-1细胞生长的影响,提取HFL-1细胞总RNA,...目的探讨溶血磷脂酸(lysophosphatidic acid,LPA)对人肺成纤维细胞(HFL-1)白细胞介素-13受体α2(IL-13Rα2)表达和Ⅰ型胶原(collagen typeⅠ,COLAⅠ)合成的影响。方法细胞培养,显微镜观察LPA对HFL-1细胞生长的影响,提取HFL-1细胞总RNA,用RT-PCR检测LPA对HFL-1细胞IL-13Rα2 mRNA和COLA I mRNA表达的影响。用免疫组化方法检测LPA和白细胞介素-13(interleukin-13,IL-13)对HFL-1细胞COLA I蛋白表达的影响。图像分析RT-PCR电泳条带和免疫组化图像,统计学处理。结果①LPA诱导HFL-1细胞IL-13Rα2 mRNA的表达,并呈时间依赖性。②1μmol.L-1 LPA刺激HFL-1细胞,IL-13Rα2 mR-NA的表达增强。③LPA作用HFL-1细胞,对IL-13Rα1的表达无影响。④LPA抑制HFL-1细胞COLA I mRNA的表达,IL-13促进COLA I mRNA的表达,LPA+IL-13混合组COLA I mRNA表达水平比LPA组高,比IL-13组低。⑤免疫组化结果与RT-PCR结果一致。结论溶血磷脂酸诱导人肺成纤维细胞表达IL-13 Rα2 mRNA,并下调人肺成纤维细胞合成COLAⅠ。展开更多
基金Supported by Grant 2010 from Tokyo MetropolisJapan
文摘AIM: To examine the expression of SphK1, an oncogenic kinase that produces sphingosine 1-phosphate (S1P), and its correlation with the expression of LPAR2, a major lysophosphatidic acid (LPA) receptor overexpressed in various cancers, in human colorectal cancer.METHODS: Real-time reverse-transcription polymerase chain reaction was used to measure the mRNA expression of SphK1, LPAR2, and the three major S1P receptors in 27 colorectal cancer samples and corresponding normal tissue samples. We also examined the correlation between the expression of SphK1 and LPAR2.RESULTS: Colorectal cancer tissue in 22 of 27 patients had higher levels of SphK1 mRNA than in normal tissue. In two-thirds of the samples, SphK1 mRNA expression was more than two-fold higher than in normal tissue. Consistent with previous reports, LPAR2 mRNA expression in 20 of 27 colorectal cancer tissue samples was higher compared to normal tissue samples. Expression profiles of all three major S1P receptors, S1PR1, S1PR2, and S1PR3, varied without any trend, with no significant difference in expression between cancer and normal tissues. A highly significant positive correlation was found between SphK1 and LPAR2 expression [Pearson’s correlation coefficient (r) = 0.784 and P < 0.01]. The mRNA levels of SphK1 and LPAR2 did not correlate with TNM stage.CONCLUSION: Our findings suggest that S1P and LPA may play important roles in the development of colorectal cancer via the upregulation of SphK1 and LPAR2, both of which could serve as new therapeutic targets in the treatment of colorectal cancer.
基金Supported by the National Natural Science Foundation of China,No.31401510
文摘Lysophosphatidic acid(LPA), a glycerophospholipid, consists of a glycerol backbone connected to a phosphate head group and an acyl chain linked to sn-1 or sn-2 position. In the circulation, LPA is in submillimolar range and mainly derived from hydrolysis of lysophosphatidylcholine, a process mediated by lysophospholipase D activity in proteins such as autotaxin(ATX). Intracellular and extracellular LPAs act as bioactive lipid mediators with diverse functions in almost every mammalian cell type. The binding of LPA to its receptors LPA1-6 activates multiple cellular processes such as migration, proliferation and survival. The production of LPA and activation of LPA receptor signaling pathways in the events of physiology and pathophysiology have attracted the interest of researchers. Results from studies using transgenic and gene knockout animals with alterations of ATX and LPA receptors genes, have revealed the roles of LPA signaling pathways in metabolic active tissues and organs. The present review was aimed to summarize recent progresses in the studies of extracellular and intracellular LPA production pathways. This includes the functional, structural and biochemical properties of ATX and LPA receptors. The potential roles of LPA production and LPA receptor signaling pathways in obesity, insulin resistance and liver fibrosis are also discussed.
基金This work was supported by the National Natural Science Foundation of China (No. 30170374)the National Basic ResearchDevelopment Program of China (No. G2000056905 2007CB512108).
文摘目的探讨溶血磷脂酸(lysophosphatidic acid,LPA)对人肺成纤维细胞(HFL-1)白细胞介素-13受体α2(IL-13Rα2)表达和Ⅰ型胶原(collagen typeⅠ,COLAⅠ)合成的影响。方法细胞培养,显微镜观察LPA对HFL-1细胞生长的影响,提取HFL-1细胞总RNA,用RT-PCR检测LPA对HFL-1细胞IL-13Rα2 mRNA和COLA I mRNA表达的影响。用免疫组化方法检测LPA和白细胞介素-13(interleukin-13,IL-13)对HFL-1细胞COLA I蛋白表达的影响。图像分析RT-PCR电泳条带和免疫组化图像,统计学处理。结果①LPA诱导HFL-1细胞IL-13Rα2 mRNA的表达,并呈时间依赖性。②1μmol.L-1 LPA刺激HFL-1细胞,IL-13Rα2 mR-NA的表达增强。③LPA作用HFL-1细胞,对IL-13Rα1的表达无影响。④LPA抑制HFL-1细胞COLA I mRNA的表达,IL-13促进COLA I mRNA的表达,LPA+IL-13混合组COLA I mRNA表达水平比LPA组高,比IL-13组低。⑤免疫组化结果与RT-PCR结果一致。结论溶血磷脂酸诱导人肺成纤维细胞表达IL-13 Rα2 mRNA,并下调人肺成纤维细胞合成COLAⅠ。
