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.
authors.affiliation: Key Laboratory of Regenerative Medicine (JNU-CUHK), Ministry of Education and Department of Developmental & Regenerative Biology, Ji Nan University, Guangzhou 510632, China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Xia
authors.affiliation: Key Laboratory of Regenerative Medicine (JNU-CUHK), Ministry of Education and Department of Developmental & Regenerative Biology, Ji Nan University, Guangzhou 510632, China.
authors.forename: Cheng-Zhou
authors.initials: CZ
authors.lastname: Mao
authors.affiliation: Key Laboratory of Regenerative Medicine (JNU-CUHK), Ministry of Education and Department of Developmental & Regenerative Biology, Ji Nan University, Guangzhou 510632, China.
authors.forename: Zhuo-Ying
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Key Laboratory of Regenerative Medicine (JNU-CUHK), Ministry of Education and Department of Developmental & Regenerative Biology, Ji Nan University, Guangzhou 510632, China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Liu
authors.affiliation: Key Laboratory of Regenerative Medicine (JNU-CUHK), Ministry of Education and Department of Developmental & Regenerative Biology, Ji Nan University, Guangzhou 510632, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wu
authors.affiliation: Key Laboratory of Regenerative Medicine (JNU-CUHK), Ministry of Education and Department of Developmental & Regenerative Biology, Ji Nan University, Guangzhou 510632, China.
authors.forename: Deng-Cheng
authors.initials: DC
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Gangwon 220-701, South Korea.
authors.forename: Kyu-Sang
authors.initials: KS
authors.lastname: Park
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Microbiology, Yonsei University Wonju College of Medicine, Wonju, Gangwon 220-701, South Korea. Electronic address: kim6@yonsei.ac.kr.
authors.forename: Soo-Ki
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Key Laboratory of Regenerative Medicine (JNU-CUHK), Ministry of Education and Department of Developmental & Regenerative Biology, Ji Nan University, Guangzhou 510632, China. Electronic address: tdongbme@jnu.edu.cn.
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Cai
authors.affiliation: Key Laboratory of Regenerative Medicine (JNU-CUHK), Ministry of Education and Department of Developmental & Regenerative Biology, Ji Nan University, Guangzhou 510632, China. Electronic address: qixufeng@jnu.edu.cn.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Qi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000494:pharmacology*; D003331:Coronary Vessels / Q000166:cytology; D042783:Endothelial Cells / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D054357:Chemokine CXCL10; C515189:Cxcr3 protein, rat; D004791:Enzyme Inhibitors; D054367:Receptors, CXCR3; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases
keywords: CMECs; CXCL10/CXCR3 pathway; Hypoxia/ischemia; Migration