The GEF Cytohesin-2/ARNO Mediates Resistin induced Phenotypic Switching in Vascular Smooth Muscle Cells
| العنوان: | The GEF Cytohesin-2/ARNO Mediates Resistin induced Phenotypic Switching in Vascular Smooth Muscle Cells |
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| المؤلفون: | Ramona Mettler, Ulrich Pohl, Hanna Mannell, Yvonn Heun, Aikaterini Lagara, Pascal Gräff, Romina Schelhorn |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) Scientific Reports |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell signaling, Cell type, Vascular smooth muscle, MAP Kinase Signaling System, Swine, p38 mitogen-activated protein kinases, Myocytes, Smooth Muscle, Phenotypic switching, lcsh:Medicine, Adipokine, 030204 cardiovascular system & hematology, Matrix metalloproteinase, Article, Gene Expression Regulation, Enzymologic, Muscle, Smooth, Vascular, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Animals, lcsh:Science, Multidisciplinary, Molecular medicine, Chemistry, GTPase-Activating Proteins, lcsh:R, Atherosclerosis, Cell biology, Cardiovascular diseases, 030104 developmental biology, Matrix Metalloproteinase 2, lcsh:Q, Resistin |
| الوصف: | The pro-inflammatory adipokine resistin induces a phenotypic switch of vascular smooth muscle cells (VSMC), a process decisive for atherosclerosis, including morphological changes, increased synthetic activity, proliferation and migration. The guanine-exchange factor ARNO (Cytohesin-2) has been shown to be important for morphological changes and migration of other cell types. In this study we dissected the role of ARNO in resistin induced VSMC phenotypic switching and signalling. Firstly, treatment with the cytohesin inhibitor Secin H3 prevented the resistin mediated induction of morphological changes in VSMC. Secondly, Secin H3 treatment as well as expression of an inactive ARNO (EK) reduced resistin induced VSMC synthetic activity, as assessed by matrix metalloproteinase 2 (MMP-2) expression, as well as the migration into a wound in vitro compared to ARNO WT expression. Thirdly, we found ARNO to influence MMP-2 expression and migration via activation of p38 MAPK and the JNK/AP-1 pathway. Interestingly, these processes were shown to be dependent on the binding of PIP3, as mutation of the ARNO PH-domain inhibited VSMC migration, MMP-2 expression as well as p38 MAPK and JNK signalling. Thus, we demonstrate that ARNO is an important link in resistin dependent cell signalling leading to morphological changes, MMP-2 production and migration of VSMC. |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74c0551afc1095922bdce84ca87d4988 https://doi.org/10.1038/s41598-020-60446-z |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....74c0551afc1095922bdce84ca87d4988 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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