Atorvastatin from target screening attenuates endothelial cell tube formation and migration by regulating urokinase receptor-related signaling pathway and F/G actin

Li Wei, Jin Shuen Chen, Hsin Ting Lin, Chung Ze Wu, Cai Mei Zheng, Yu Ching Chang, Li Chien Chang, Yuh Feng Lin

研究成果: 雜誌貢獻文章

3 引文 (Scopus)

摘要

Background Angiogenesis and cytoskeletal transformation are common denominators of many pathological developments. The relationship between angiogenesis, urokinase plasminogen activator receptor (uPAR) signaling pathway, and cytoskeletal transformation is still unknown. In this study, a pGL3-uPAR promoter reporter system combined with Bio-Plex mRNA analysis was established for discovering uPAR modulators to analyze this interconnection. Methods After screening a set of clinically used drugs, atorvastatin (Ator) was found to significantly affect uPAR expression and its ideal dose, 1 μM, was determined for cell study. Mouse endothelial cell (mEC) models, including tube formation for angiogenesis and wound healing assay for migration, were employed to test the effects on angiogenesis and cytoskeletal transformation with (Group Ator) and without (Group C) the treatment of Ator. Results The mEC tube formation and migration was significantly decreased in Group Ator. Regarding cytoskeleton changes, the ratio of F/G actin by Western blotting and the assembly of F-actin (lamellipodia) by immunofluorescence were attenuated. Furthermore, uPAR and all uPAR-related factors, including integrin α5β3, phosphorylated-focal adhesion kinase, and Rac, revealed a significant reduction when compared with Group C. Conclusion We conclude that close regulatory machinery spans angiogenesis, uPAR signaling, and cytoskeletal transformation, and that uPAR modulator Ator can decrease the reorganization of actin cytoskeleton, which may lead to a new approach in angiogenesis.
原文英語
頁(從 - 到)86-95
頁數10
期刊Journal of the Chinese Medical Association
80
發行號2
DOIs
出版狀態已發佈 - 二月 1 2017

指紋

Urokinase Plasminogen Activator Receptors
Urokinase-Type Plasminogen Activator
Actins
Endothelial Cells
Focal Adhesion Protein-Tyrosine Kinases
Pseudopodia
Atorvastatin Calcium
Cytoskeleton
Actin Cytoskeleton
Integrins
Wound Healing
Fluorescent Antibody Technique
Western Blotting
Messenger RNA

ASJC Scopus subject areas

  • Medicine(all)

引用此文

@article{95a4627ff2d2426d8fd0922a75f3e854,
title = "Atorvastatin from target screening attenuates endothelial cell tube formation and migration by regulating urokinase receptor-related signaling pathway and F/G actin",
abstract = "Background Angiogenesis and cytoskeletal transformation are common denominators of many pathological developments. The relationship between angiogenesis, urokinase plasminogen activator receptor (uPAR) signaling pathway, and cytoskeletal transformation is still unknown. In this study, a pGL3-uPAR promoter reporter system combined with Bio-Plex mRNA analysis was established for discovering uPAR modulators to analyze this interconnection. Methods After screening a set of clinically used drugs, atorvastatin (Ator) was found to significantly affect uPAR expression and its ideal dose, 1 μM, was determined for cell study. Mouse endothelial cell (mEC) models, including tube formation for angiogenesis and wound healing assay for migration, were employed to test the effects on angiogenesis and cytoskeletal transformation with (Group Ator) and without (Group C) the treatment of Ator. Results The mEC tube formation and migration was significantly decreased in Group Ator. Regarding cytoskeleton changes, the ratio of F/G actin by Western blotting and the assembly of F-actin (lamellipodia) by immunofluorescence were attenuated. Furthermore, uPAR and all uPAR-related factors, including integrin α5β3, phosphorylated-focal adhesion kinase, and Rac, revealed a significant reduction when compared with Group C. Conclusion We conclude that close regulatory machinery spans angiogenesis, uPAR signaling, and cytoskeletal transformation, and that uPAR modulator Ator can decrease the reorganization of actin cytoskeleton, which may lead to a new approach in angiogenesis.",
keywords = "angiogenesis, atorvastatin, cytoskeleton, urokinase receptor",
author = "Li Wei and Chen, {Jin Shuen} and Lin, {Hsin Ting} and Wu, {Chung Ze} and Zheng, {Cai Mei} and Chang, {Yu Ching} and Chang, {Li Chien} and Lin, {Yuh Feng}",
year = "2017",
month = "2",
day = "1",
doi = "10.1016/j.jcma.2016.02.015",
language = "English",
volume = "80",
pages = "86--95",
journal = "Journal of the Chinese Medical Association",
issn = "1726-4901",
publisher = "Elsevier Taiwan LLC",
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TY - JOUR

T1 - Atorvastatin from target screening attenuates endothelial cell tube formation and migration by regulating urokinase receptor-related signaling pathway and F/G actin

AU - Wei, Li

AU - Chen, Jin Shuen

AU - Lin, Hsin Ting

AU - Wu, Chung Ze

AU - Zheng, Cai Mei

AU - Chang, Yu Ching

AU - Chang, Li Chien

AU - Lin, Yuh Feng

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Background Angiogenesis and cytoskeletal transformation are common denominators of many pathological developments. The relationship between angiogenesis, urokinase plasminogen activator receptor (uPAR) signaling pathway, and cytoskeletal transformation is still unknown. In this study, a pGL3-uPAR promoter reporter system combined with Bio-Plex mRNA analysis was established for discovering uPAR modulators to analyze this interconnection. Methods After screening a set of clinically used drugs, atorvastatin (Ator) was found to significantly affect uPAR expression and its ideal dose, 1 μM, was determined for cell study. Mouse endothelial cell (mEC) models, including tube formation for angiogenesis and wound healing assay for migration, were employed to test the effects on angiogenesis and cytoskeletal transformation with (Group Ator) and without (Group C) the treatment of Ator. Results The mEC tube formation and migration was significantly decreased in Group Ator. Regarding cytoskeleton changes, the ratio of F/G actin by Western blotting and the assembly of F-actin (lamellipodia) by immunofluorescence were attenuated. Furthermore, uPAR and all uPAR-related factors, including integrin α5β3, phosphorylated-focal adhesion kinase, and Rac, revealed a significant reduction when compared with Group C. Conclusion We conclude that close regulatory machinery spans angiogenesis, uPAR signaling, and cytoskeletal transformation, and that uPAR modulator Ator can decrease the reorganization of actin cytoskeleton, which may lead to a new approach in angiogenesis.

AB - Background Angiogenesis and cytoskeletal transformation are common denominators of many pathological developments. The relationship between angiogenesis, urokinase plasminogen activator receptor (uPAR) signaling pathway, and cytoskeletal transformation is still unknown. In this study, a pGL3-uPAR promoter reporter system combined with Bio-Plex mRNA analysis was established for discovering uPAR modulators to analyze this interconnection. Methods After screening a set of clinically used drugs, atorvastatin (Ator) was found to significantly affect uPAR expression and its ideal dose, 1 μM, was determined for cell study. Mouse endothelial cell (mEC) models, including tube formation for angiogenesis and wound healing assay for migration, were employed to test the effects on angiogenesis and cytoskeletal transformation with (Group Ator) and without (Group C) the treatment of Ator. Results The mEC tube formation and migration was significantly decreased in Group Ator. Regarding cytoskeleton changes, the ratio of F/G actin by Western blotting and the assembly of F-actin (lamellipodia) by immunofluorescence were attenuated. Furthermore, uPAR and all uPAR-related factors, including integrin α5β3, phosphorylated-focal adhesion kinase, and Rac, revealed a significant reduction when compared with Group C. Conclusion We conclude that close regulatory machinery spans angiogenesis, uPAR signaling, and cytoskeletal transformation, and that uPAR modulator Ator can decrease the reorganization of actin cytoskeleton, which may lead to a new approach in angiogenesis.

KW - angiogenesis

KW - atorvastatin

KW - cytoskeleton

KW - urokinase receptor

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