Gax inhibits perivascular preadipocyte biofunction mediated by IGF-1 induced FAK/Pyk2 and ERK2 cooperative pathways
| Autor: | Ping Liu, Haijia Xu, Feng Kong, Yungi Jiang, Juan Meng, Jinbo Feng, Qinghua Lu |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty MAP Kinase Signaling System medicine.medical_treatment Muscle Proteins Apoptosis Biology Transfection Flow cytometry Rats Sprague-Dawley chemistry.chemical_compound Downregulation and upregulation Cell Movement Internal medicine Adipocyte medicine Adipocytes Cell Adhesion Animals Humans Insulin-Like Growth Factor I RNA Small Interfering Protein Kinase Inhibitors Cell Proliferation Homeodomain Proteins Mitogen-Activated Protein Kinase 1 Messenger RNA medicine.diagnostic_test Growth factor Cell Cycle Cell Biology Flow Cytometry Cell biology Blot Endocrinology Focal Adhesion Kinase 2 chemistry Adipose Tissue Signal transduction |
| Zdroj: | Cellular signalling. 26(12) |
| ISSN: | 1873-3913 |
| Popis: | Perivascular adipocyte (PVAC) biofunctions were closely related to cardiovascular diseases; its specific biological mechanisms remained unclear. How to adjust PVAC functions of vascular cells is an important topic. The present study was designed to investigate whether FAK/Pyk2 and ERK1/2 MAPK signaling pathways participate in PVAC functions, which is activated by insulin-like growth factor 1(IGF-1) and inhibited by Gax. PVACs isolated from perivascular adipocyte were cultured, dedifferentiated, and stimulated with 10nM IGF-I. Cellular function experiments showed that IGF-1 promoted PVAC proliferation, adhesion, and migration. However Gax weakened IGF-1-mediated these function. Flow cytometry demonstrated that IGF-1 increased PVACs percent of S phase and decreased the percent of G0/G1 phase and apoptotic cells. While, Gax decreased the percent of S phase cells and increased those of G0-G1 phase and apoptotic cells. Western blotting and RT-PCR revealed that IGF-1 activated FAK/Pyk2 and ERK1/2 signaling pathways, upregulated the mRNA and protein expression of FAK, Pyk2, and ERK1/2, and suppressed p53 expression. Reversely, Gax lowered the expression of these signaling proteins and increased p53 expression. Therefore, IGF-1 mediated FAK/Pyk2 and ERK1/2 pathways to augment PVAC functions; Gax effectively counteracted these effects of IGF-1, repressed PVAC activities, and increased the cell apoptosis. Our findings suggested that FAK/Pyk2 and ERK1/2 cooperative activation mediated by IGF-1 is essential for PVAC functions, and Gax is a promising candidate gene to interfere with these signaling pathways and inhibit PVAC functions. |
| Databáze: | OpenAIRE |
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