author_facet Jin, Cheng-wei
Wang, Hui
Chen, Yan-qing
Tang, Meng-xiong
Fan, Guan-qi
Wang, Zhi-hao
Li, Li
Zhang, Yun
Zhang, Wei
Zhong, Ming
Jin, Cheng-wei
Wang, Hui
Chen, Yan-qing
Tang, Meng-xiong
Fan, Guan-qi
Wang, Zhi-hao
Li, Li
Zhang, Yun
Zhang, Wei
Zhong, Ming
author Jin, Cheng-wei
Wang, Hui
Chen, Yan-qing
Tang, Meng-xiong
Fan, Guan-qi
Wang, Zhi-hao
Li, Li
Zhang, Yun
Zhang, Wei
Zhong, Ming
spellingShingle Jin, Cheng-wei
Wang, Hui
Chen, Yan-qing
Tang, Meng-xiong
Fan, Guan-qi
Wang, Zhi-hao
Li, Li
Zhang, Yun
Zhang, Wei
Zhong, Ming
Cellular Physiology and Biochemistry
Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
Physiology
author_sort jin, cheng-wei
spelling Jin, Cheng-wei Wang, Hui Chen, Yan-qing Tang, Meng-xiong Fan, Guan-qi Wang, Zhi-hao Li, Li Zhang, Yun Zhang, Wei Zhong, Ming 1015-8987 1421-9778 S. Karger AG Physiology http://dx.doi.org/10.1159/000373940 <jats:p>Background/Aims: Growth arrest-specific protein 6 (Gas6) is a cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix. Previous studies have confirmed that Gas6 is involved in certain pathophysiological processes of the cardiovascular system through binding to its receptor, Axl. In the present study, we investigated the role of Gas6 in cellular senescence and explored the mechanisms underlying its activity. Methods: We used vascular smooth muscle cells (VSMCs) to create two cellular senescence models, one for replicative senescence (RS) and one for induced senescence (IS), to test the hypothesis that Gas6 delays senescence. Results: Gas6-treated cells appear relatively younger compared with non-Gas6-treated cells. In particular, Gas6-treated cells displayed decreased staining for SA-β-Gal, fewer G1 phase cells, and decreased levels of p16INK4a and p21Cip1 expression; conversely, Gas6-treated cells displayed more S phase cells and significantly increased proliferation indexes. Furthermore, in both the IS and RS models with Gas6 treatment, the levels of PI3K, p-Akt, and p-FoxO3a decreased following Axl inhibition by R428; similarly, the levels of p-Akt and p-FoxO3a also decreased following PI3K inhibition by LY294002. Conclusion: Gas6/Axl signaling is essential for delaying the cellular senescence process regulated by the PI3K/Akt/FoxO signaling pathway.</jats:p> Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway Cellular Physiology and Biochemistry
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title Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_unstemmed Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_full Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_fullStr Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_full_unstemmed Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_short Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_sort gas6 delays senescence in vascular smooth muscle cells through the pi3k/ akt/foxo signaling pathway
topic Physiology
url http://dx.doi.org/10.1159/000373940
publishDate 2015
physical 1151-1166
description <jats:p>Background/Aims: Growth arrest-specific protein 6 (Gas6) is a cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix. Previous studies have confirmed that Gas6 is involved in certain pathophysiological processes of the cardiovascular system through binding to its receptor, Axl. In the present study, we investigated the role of Gas6 in cellular senescence and explored the mechanisms underlying its activity. Methods: We used vascular smooth muscle cells (VSMCs) to create two cellular senescence models, one for replicative senescence (RS) and one for induced senescence (IS), to test the hypothesis that Gas6 delays senescence. Results: Gas6-treated cells appear relatively younger compared with non-Gas6-treated cells. In particular, Gas6-treated cells displayed decreased staining for SA-β-Gal, fewer G1 phase cells, and decreased levels of p16INK4a and p21Cip1 expression; conversely, Gas6-treated cells displayed more S phase cells and significantly increased proliferation indexes. Furthermore, in both the IS and RS models with Gas6 treatment, the levels of PI3K, p-Akt, and p-FoxO3a decreased following Axl inhibition by R428; similarly, the levels of p-Akt and p-FoxO3a also decreased following PI3K inhibition by LY294002. Conclusion: Gas6/Axl signaling is essential for delaying the cellular senescence process regulated by the PI3K/Akt/FoxO signaling pathway.</jats:p>
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author Jin, Cheng-wei, Wang, Hui, Chen, Yan-qing, Tang, Meng-xiong, Fan, Guan-qi, Wang, Zhi-hao, Li, Li, Zhang, Yun, Zhang, Wei, Zhong, Ming
author_facet Jin, Cheng-wei, Wang, Hui, Chen, Yan-qing, Tang, Meng-xiong, Fan, Guan-qi, Wang, Zhi-hao, Li, Li, Zhang, Yun, Zhang, Wei, Zhong, Ming, Jin, Cheng-wei, Wang, Hui, Chen, Yan-qing, Tang, Meng-xiong, Fan, Guan-qi, Wang, Zhi-hao, Li, Li, Zhang, Yun, Zhang, Wei, Zhong, Ming
author_sort jin, cheng-wei
container_issue 3
container_start_page 1151
container_title Cellular Physiology and Biochemistry
container_volume 35
description <jats:p>Background/Aims: Growth arrest-specific protein 6 (Gas6) is a cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix. Previous studies have confirmed that Gas6 is involved in certain pathophysiological processes of the cardiovascular system through binding to its receptor, Axl. In the present study, we investigated the role of Gas6 in cellular senescence and explored the mechanisms underlying its activity. Methods: We used vascular smooth muscle cells (VSMCs) to create two cellular senescence models, one for replicative senescence (RS) and one for induced senescence (IS), to test the hypothesis that Gas6 delays senescence. Results: Gas6-treated cells appear relatively younger compared with non-Gas6-treated cells. In particular, Gas6-treated cells displayed decreased staining for SA-β-Gal, fewer G1 phase cells, and decreased levels of p16INK4a and p21Cip1 expression; conversely, Gas6-treated cells displayed more S phase cells and significantly increased proliferation indexes. Furthermore, in both the IS and RS models with Gas6 treatment, the levels of PI3K, p-Akt, and p-FoxO3a decreased following Axl inhibition by R428; similarly, the levels of p-Akt and p-FoxO3a also decreased following PI3K inhibition by LY294002. Conclusion: Gas6/Axl signaling is essential for delaying the cellular senescence process regulated by the PI3K/Akt/FoxO signaling pathway.</jats:p>
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spelling Jin, Cheng-wei Wang, Hui Chen, Yan-qing Tang, Meng-xiong Fan, Guan-qi Wang, Zhi-hao Li, Li Zhang, Yun Zhang, Wei Zhong, Ming 1015-8987 1421-9778 S. Karger AG Physiology http://dx.doi.org/10.1159/000373940 <jats:p>Background/Aims: Growth arrest-specific protein 6 (Gas6) is a cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix. Previous studies have confirmed that Gas6 is involved in certain pathophysiological processes of the cardiovascular system through binding to its receptor, Axl. In the present study, we investigated the role of Gas6 in cellular senescence and explored the mechanisms underlying its activity. Methods: We used vascular smooth muscle cells (VSMCs) to create two cellular senescence models, one for replicative senescence (RS) and one for induced senescence (IS), to test the hypothesis that Gas6 delays senescence. Results: Gas6-treated cells appear relatively younger compared with non-Gas6-treated cells. In particular, Gas6-treated cells displayed decreased staining for SA-β-Gal, fewer G1 phase cells, and decreased levels of p16INK4a and p21Cip1 expression; conversely, Gas6-treated cells displayed more S phase cells and significantly increased proliferation indexes. Furthermore, in both the IS and RS models with Gas6 treatment, the levels of PI3K, p-Akt, and p-FoxO3a decreased following Axl inhibition by R428; similarly, the levels of p-Akt and p-FoxO3a also decreased following PI3K inhibition by LY294002. Conclusion: Gas6/Axl signaling is essential for delaying the cellular senescence process regulated by the PI3K/Akt/FoxO signaling pathway.</jats:p> Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway Cellular Physiology and Biochemistry
spellingShingle Jin, Cheng-wei, Wang, Hui, Chen, Yan-qing, Tang, Meng-xiong, Fan, Guan-qi, Wang, Zhi-hao, Li, Li, Zhang, Yun, Zhang, Wei, Zhong, Ming, Cellular Physiology and Biochemistry, Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway, Physiology
title Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_full Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_fullStr Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_full_unstemmed Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_short Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
title_sort gas6 delays senescence in vascular smooth muscle cells through the pi3k/ akt/foxo signaling pathway
title_unstemmed Gas6 Delays Senescence in Vascular Smooth Muscle Cells through the PI3K/ Akt/FoxO Signaling Pathway
topic Physiology
url http://dx.doi.org/10.1159/000373940