title: Hydrogen Sulfide Recruits Macrophage Migration by Integrin β1-Src-FAK/Pyk2-Rac Pathway in Myocardial Infarction.
abstract: Myocardial infarction (MI) triggers an inflammatory reaction, in which macrophages are of key importance for tissue repairing. Infiltration and/or migration of macrophages into the infarct area early after MI is critical for infarct healing, vascularization, and cardiac function. Hydrogen sulfide (H2S) has been demonstrated to possess cardioprotective effects post MI and during the progress of cardiac remodeling. However, the specific molecular and cellular mechanisms involved in macrophage recruitment by H2S remain to be identified. In this study, the NaHS (exogenous sources of H2S) treatment exerted an increased infiltration of macrophages into the infarcted myocardium at early stage of MI cardiac tissues in both wild type (WT) and cystathionine-γ-lyase-knockout (CSE-KO) mice. And NaHS accelerated the migration of macrophage cells in vitro. While, the inhibitors not only significantly diminished the migratory ability in response to NaHS, but also blocked the activation of phospho-Src, -Pyk2, -FAK(397), and -FAK(925). Furthermore, NaHS induced the internalization of integrin β1 on macrophage surface, but, integrin β1 silencing inhibited macrophage migration and Src signaling activation. These results indicate that H2S may have the potential as an anti-infarct of MI by governing macrophage migration, which was achieved by accelerating internalization of integrin β1 and activating downstream Src-FAK/Pyk2-Rac pathway.
authors.affiliation: Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Miao
authors.affiliation: Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xin
authors.affiliation: Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.affiliation: Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, School of Pharmacy and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Department of Pharmacology, School of Pharmacy, Macau University of Science &Technology, Macau, China.
authors.forename: Yi-Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D019012:Integrin beta1 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D019012:Integrin beta1; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide