The differentiation expression of LPLs receptors in Different Endothelial Cells
碩士 === 國立臺灣大學 === 動物學研究所 === 92 === Abstract Lysophospatidic acid (LPA) and Sphingosine-1-phosphate (S1P) are two kinds of low molecular weight lysophospholipids (LPLs), stored primarily in platelets in the plasma and serum. During inflammation, S1P and LPA would be released fr...
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ndltd-TW-092NTU003120032015-10-13T13:27:34Z http://ndltd.ncl.edu.tw/handle/60150149238443794789 The differentiation expression of LPLs receptors in Different Endothelial Cells 水解磷酸脂接受器於不同內皮細胞表達之特異性研究 Lee Yu-Wei 李玉葳 碩士 國立臺灣大學 動物學研究所 92 Abstract Lysophospatidic acid (LPA) and Sphingosine-1-phosphate (S1P) are two kinds of low molecular weight lysophospholipids (LPLs), stored primarily in platelets in the plasma and serum. During inflammation, S1P and LPA would be released from activating platelets. They are capable of regulating multiple aspects of angiogenesis and vessel maturation in vitro, including cell chemotaxis, differentiation, proliferation, migration, survival and capillary morphogenesis. The physiological functions of S1P and LPA are mediated by ligating with members of G-protein coupled receptors: S1P1 through 5 and LPA1 through 3,which could then activate more than three different heterotrimeric GTP proteins─including Gi、Gq and G(12/13). The expression of LPLs receptors in endothelial cells would affect the S1P and LPA functions. There is no previous evidence showing the expression profiles of S1P and LPA receptors profiles in endothelial cells from various species. In this study, we aim to investigate the expression of S1P and LPA receptors in different endothelial cells isolated from human, rat, mouse and bovine. Our results indicate that endothelial cells from various species express different LPLs receptors. Even in the same species but different cells, such as HUVECs, EAHY926 cells and HAECs from human, also have different LPLs receptors profiles. Studies by other groups used HUVECs as a model system to investigate almost every aspect of endothelial cells functions. Based on the cultural condition in BAECs require less reagent than HUVECs, we were first test if BAECs is a proper endothelial cells system to investigate S1P functions. Our results suggest that S1P induce BAECs wound healing effect and chemotactic migration in a dose dependent manner. These results indicate that BAEC is an appropriate model to investigate LPA and S1P functions. Furthermore, previous studies in our lab had showed that S1P treatment would affect PECAM-1 localization on cell surface of HUVECs, but the total PECAM-1 expression were not affected. PECAM-1 is an ITIM-bearing Ig superfamily adhesion molecule, express abundantly on endothelial cells, and various hemopoietic cell types. By using immunoprecipitation and western blot, we also demonstrated S1P induce PECAM-1 tyrosine phosphorylation in BAECs and subsequently the association of SHP-2 had also increased. By using specific kinase inhibitors, we identify a unique Src family kinase dependent signaling pathway activated by S1P and subsequently induced PECAM-1 tyrosine phosphorylation. These results suggest that S1P may play a very important role in regulating PECAM-1 mediated endothelial cells physiological functions through a Src family kinase dependent signaling pathway. Lee Hsinyu 李心予 2004 學位論文 ; thesis 72 zh-TW |
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碩士 === 國立臺灣大學 === 動物學研究所 === 92 === Abstract
Lysophospatidic acid (LPA) and Sphingosine-1-phosphate (S1P) are two kinds of low molecular weight lysophospholipids (LPLs), stored primarily in platelets in the plasma and serum. During inflammation, S1P and LPA would be released from activating platelets. They are capable of regulating multiple aspects of angiogenesis and vessel maturation in vitro, including cell chemotaxis, differentiation, proliferation, migration, survival and capillary morphogenesis. The physiological functions of S1P and LPA are mediated by ligating with members of G-protein coupled receptors: S1P1 through 5 and LPA1 through 3,which could then activate more than three different heterotrimeric GTP proteins─including Gi、Gq and G(12/13). The expression of LPLs receptors in endothelial cells would affect the S1P and LPA functions. There is no previous evidence showing the expression profiles of S1P and LPA receptors profiles in endothelial cells from various species. In this study, we aim to investigate the expression of S1P and LPA receptors in different endothelial cells isolated from human, rat, mouse and bovine. Our results indicate that endothelial cells from various species express different LPLs receptors. Even in the same species but different cells, such as HUVECs, EAHY926 cells and HAECs from human, also have different LPLs receptors profiles. Studies by other groups used HUVECs as a model system to investigate almost every aspect of endothelial cells functions. Based on the cultural condition in BAECs require less reagent than HUVECs, we were first test if BAECs is a proper endothelial cells system to investigate S1P functions. Our results suggest that S1P induce BAECs wound healing effect and chemotactic migration in a dose dependent manner. These results indicate that BAEC is an appropriate model to investigate LPA and S1P functions. Furthermore, previous studies in our lab had showed that S1P treatment would affect PECAM-1 localization on cell surface of HUVECs, but the total PECAM-1 expression were not affected. PECAM-1 is an ITIM-bearing Ig superfamily adhesion molecule, express abundantly on endothelial cells, and various hemopoietic cell types. By using immunoprecipitation and western blot, we also demonstrated S1P induce PECAM-1 tyrosine phosphorylation in BAECs and subsequently the association of SHP-2 had also increased. By using specific kinase inhibitors, we identify a unique Src family kinase dependent signaling pathway activated by S1P and subsequently induced PECAM-1 tyrosine phosphorylation. These results suggest that S1P may play a very important role in regulating PECAM-1 mediated endothelial cells physiological functions through a Src family kinase dependent signaling pathway.
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author2 |
Lee Hsinyu |
author_facet |
Lee Hsinyu Lee Yu-Wei 李玉葳 |
author |
Lee Yu-Wei 李玉葳 |
spellingShingle |
Lee Yu-Wei 李玉葳 The differentiation expression of LPLs receptors in Different Endothelial Cells |
author_sort |
Lee Yu-Wei |
title |
The differentiation expression of LPLs receptors in Different Endothelial Cells |
title_short |
The differentiation expression of LPLs receptors in Different Endothelial Cells |
title_full |
The differentiation expression of LPLs receptors in Different Endothelial Cells |
title_fullStr |
The differentiation expression of LPLs receptors in Different Endothelial Cells |
title_full_unstemmed |
The differentiation expression of LPLs receptors in Different Endothelial Cells |
title_sort |
differentiation expression of lpls receptors in different endothelial cells |
publishDate |
2004 |
url |
http://ndltd.ncl.edu.tw/handle/60150149238443794789 |
work_keys_str_mv |
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