The CXCL10/CXCR3 axis promotes cardiac microvascular endothelial cell migration via the p38/FAK pathway in a proliferation-independent manner

Jing Bo Xia; Cheng Zhou Mao; Zhuo Ying Chen; Guang Hui Liu; Hai Yan Wu; Deng Cheng Zhou; Kyu Sang Park; Hui Zhao; Soo Ki Kim; Dong Qing Cai; Xu Feng Qi

doi:10.1016/j.yexmp.2016.01.010

The CXCL10/CXCR3 axis promotes cardiac microvascular endothelial cell migration via the p38/FAK pathway in a proliferation-independent manner

Jing Bo Xia, Cheng Zhou Mao, Zhuo Ying Chen, Guang Hui Liu, Hai Yan Wu, Deng Cheng Zhou, Kyu Sang Park, Hui Zhao, Soo Ki Kim, Dong Qing Cai, Xu Feng Qi

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

CXCL10 is a chemokine with potent chemotactic activity for immune and non-immune cells expressing its receptor CXCR3. Previous studies have demonstrated that CXCL10 is involved in myocardial infarction. However, the role of CXCL10 in cardiac microvascular endothelial cell (CMEC) regulation and related mechanisms remains unclear. In this study, we investigated the effects of CXCL10 on the CMEC migration and explored its potential molecular mechanism by wound healing, cell proliferation and viability analysis. Furthermore, migration-related signaling pathways, including FAK, Erk, p38 and Smad, were examined by Western blotting. We found that CXCL10 significantly promotes CMEC migration under normal conditions and during hypoxia/ischemia. However, no significant differences in CMEC proliferation and viability were observed with or without CXCL10 treatment. CXCL10-mediated CMEC migration was greatly blocked by treatment with an anti-CXCR3 antibody. Although CXCL10 treatment promoted phosphorylation and activation of the FAK, Erk, and p38 pathways during hypoxia/ischemia, CXCL10-mediated CMEC migration was significantly blocked by p38 and FAK inhibitors, but not by an Erk inhibitor. Furthermore, CXCL10-mediated FAK activation was suppressed by the p38 inhibitor. These findings indicated that the CXCL10/CXCR3 pathway promotes the migration of CMECs under normal conditions and during hypoxia/ischemia in a proliferation-independent manner, at least in part, through regulation of the p38/FAK pathways.

Original language	English
Pages (from-to)	257-265
Number of pages	9
Journal	Experimental and Molecular Pathology
Volume	100
Issue number	2
DOIs	https://doi.org/10.1016/j.yexmp.2016.01.010
Publication status	Published - 2016 Apr 1

Bibliographical note

Funding Information:
This work was supported by grants from NSFC ( 81270183 , 81570222 ), Guangdong Natural Science Funds for Distinguished Young Scholar ( 2014A030306011 ), Guangdong Science and Technology Planning Project ( 2014A050503043 ), Guangdong Natural Science Foundation ( S2013010013598 ), New Star of Pearl River on Science and Technology of Guangzhou ( 2014J2200002 ), Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry ( 2013-693 ), and the Top Young Talents of Guangdong Province Special Support Program ( 87315007 ), China.

Publisher Copyright:
© 2016 Elsevier Inc.

All Science Journal Classification (ASJC) codes

Pathology and Forensic Medicine
Molecular Biology
Clinical Biochemistry

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10.1016/j.yexmp.2016.01.010

Cite this

Xia, J. B., Mao, C. Z., Chen, Z. Y., Liu, G. H., Wu, H. Y., Zhou, D. C., Park, K. S., Zhao, H., Kim, S. K., Cai, D. Q., & Qi, X. F. (2016). The CXCL10/CXCR3 axis promotes cardiac microvascular endothelial cell migration via the p38/FAK pathway in a proliferation-independent manner. Experimental and Molecular Pathology, 100(2), 257-265. https://doi.org/10.1016/j.yexmp.2016.01.010

@article{1eeaf1e1123447278362df381228177b,

title = "The CXCL10/CXCR3 axis promotes cardiac microvascular endothelial cell migration via the p38/FAK pathway in a proliferation-independent manner",

abstract = "CXCL10 is a chemokine with potent chemotactic activity for immune and non-immune cells expressing its receptor CXCR3. Previous studies have demonstrated that CXCL10 is involved in myocardial infarction. However, the role of CXCL10 in cardiac microvascular endothelial cell (CMEC) regulation and related mechanisms remains unclear. In this study, we investigated the effects of CXCL10 on the CMEC migration and explored its potential molecular mechanism by wound healing, cell proliferation and viability analysis. Furthermore, migration-related signaling pathways, including FAK, Erk, p38 and Smad, were examined by Western blotting. We found that CXCL10 significantly promotes CMEC migration under normal conditions and during hypoxia/ischemia. However, no significant differences in CMEC proliferation and viability were observed with or without CXCL10 treatment. CXCL10-mediated CMEC migration was greatly blocked by treatment with an anti-CXCR3 antibody. Although CXCL10 treatment promoted phosphorylation and activation of the FAK, Erk, and p38 pathways during hypoxia/ischemia, CXCL10-mediated CMEC migration was significantly blocked by p38 and FAK inhibitors, but not by an Erk inhibitor. Furthermore, CXCL10-mediated FAK activation was suppressed by the p38 inhibitor. These findings indicated that the CXCL10/CXCR3 pathway promotes the migration of CMECs under normal conditions and during hypoxia/ischemia in a proliferation-independent manner, at least in part, through regulation of the p38/FAK pathways.",

author = "Xia, {Jing Bo} and Mao, {Cheng Zhou} and Chen, {Zhuo Ying} and Liu, {Guang Hui} and Wu, {Hai Yan} and Zhou, {Deng Cheng} and Park, {Kyu Sang} and Hui Zhao and Kim, {Soo Ki} and Cai, {Dong Qing} and Qi, {Xu Feng}",

note = "Funding Information: This work was supported by grants from NSFC ( 81270183 , 81570222 ), Guangdong Natural Science Funds for Distinguished Young Scholar ( 2014A030306011 ), Guangdong Science and Technology Planning Project ( 2014A050503043 ), Guangdong Natural Science Foundation ( S2013010013598 ), New Star of Pearl River on Science and Technology of Guangzhou ( 2014J2200002 ), Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry ( 2013-693 ), and the Top Young Talents of Guangdong Province Special Support Program ( 87315007 ), China. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

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day = "1",

doi = "10.1016/j.yexmp.2016.01.010",

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T1 - The CXCL10/CXCR3 axis promotes cardiac microvascular endothelial cell migration via the p38/FAK pathway in a proliferation-independent manner

AU - Xia, Jing Bo

AU - Mao, Cheng Zhou

AU - Chen, Zhuo Ying

AU - Liu, Guang Hui

AU - Wu, Hai Yan

AU - Zhou, Deng Cheng

AU - Park, Kyu Sang

AU - Zhao, Hui

AU - Kim, Soo Ki

AU - Cai, Dong Qing

AU - Qi, Xu Feng

N1 - Funding Information: This work was supported by grants from NSFC ( 81270183 , 81570222 ), Guangdong Natural Science Funds for Distinguished Young Scholar ( 2014A030306011 ), Guangdong Science and Technology Planning Project ( 2014A050503043 ), Guangdong Natural Science Foundation ( S2013010013598 ), New Star of Pearl River on Science and Technology of Guangzhou ( 2014J2200002 ), Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry ( 2013-693 ), and the Top Young Talents of Guangdong Province Special Support Program ( 87315007 ), China. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - CXCL10 is a chemokine with potent chemotactic activity for immune and non-immune cells expressing its receptor CXCR3. Previous studies have demonstrated that CXCL10 is involved in myocardial infarction. However, the role of CXCL10 in cardiac microvascular endothelial cell (CMEC) regulation and related mechanisms remains unclear. In this study, we investigated the effects of CXCL10 on the CMEC migration and explored its potential molecular mechanism by wound healing, cell proliferation and viability analysis. Furthermore, migration-related signaling pathways, including FAK, Erk, p38 and Smad, were examined by Western blotting. We found that CXCL10 significantly promotes CMEC migration under normal conditions and during hypoxia/ischemia. However, no significant differences in CMEC proliferation and viability were observed with or without CXCL10 treatment. CXCL10-mediated CMEC migration was greatly blocked by treatment with an anti-CXCR3 antibody. Although CXCL10 treatment promoted phosphorylation and activation of the FAK, Erk, and p38 pathways during hypoxia/ischemia, CXCL10-mediated CMEC migration was significantly blocked by p38 and FAK inhibitors, but not by an Erk inhibitor. Furthermore, CXCL10-mediated FAK activation was suppressed by the p38 inhibitor. These findings indicated that the CXCL10/CXCR3 pathway promotes the migration of CMECs under normal conditions and during hypoxia/ischemia in a proliferation-independent manner, at least in part, through regulation of the p38/FAK pathways.

AB - CXCL10 is a chemokine with potent chemotactic activity for immune and non-immune cells expressing its receptor CXCR3. Previous studies have demonstrated that CXCL10 is involved in myocardial infarction. However, the role of CXCL10 in cardiac microvascular endothelial cell (CMEC) regulation and related mechanisms remains unclear. In this study, we investigated the effects of CXCL10 on the CMEC migration and explored its potential molecular mechanism by wound healing, cell proliferation and viability analysis. Furthermore, migration-related signaling pathways, including FAK, Erk, p38 and Smad, were examined by Western blotting. We found that CXCL10 significantly promotes CMEC migration under normal conditions and during hypoxia/ischemia. However, no significant differences in CMEC proliferation and viability were observed with or without CXCL10 treatment. CXCL10-mediated CMEC migration was greatly blocked by treatment with an anti-CXCR3 antibody. Although CXCL10 treatment promoted phosphorylation and activation of the FAK, Erk, and p38 pathways during hypoxia/ischemia, CXCL10-mediated CMEC migration was significantly blocked by p38 and FAK inhibitors, but not by an Erk inhibitor. Furthermore, CXCL10-mediated FAK activation was suppressed by the p38 inhibitor. These findings indicated that the CXCL10/CXCR3 pathway promotes the migration of CMECs under normal conditions and during hypoxia/ischemia in a proliferation-independent manner, at least in part, through regulation of the p38/FAK pathways.

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AN - SCOPUS:84956654695

SN - 0014-4800

VL - 100

SP - 257

EP - 265

JO - Experimental and Molecular Pathology

JF - Experimental and Molecular Pathology

IS - 2

ER -

The CXCL10/CXCR3 axis promotes cardiac microvascular endothelial cell migration via the p38/FAK pathway in a proliferation-independent manner

Abstract

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