title: Gax inhibits perivascular preadipocyte biofunction mediated by IGF-1 induced FAK/Pyk2 and ERK2 cooperative pathways.
abstract: 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.
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong 250033, PR China. Electronic address: lping@sdu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: The Central Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Feng
authors.affiliation: Central Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong 250033, PR China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Weihai Wendeng Central Hospital, Weihai, Shandong 264400, PR China.
authors.forename: Haijia
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong 250033, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong 250033, PR China.
authors.forename: Yungi
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000098:blood supply*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D018398:Homeodomain Proteins; C081336:Meox2 protein, rat; D009124:Muscle Proteins; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I; D051418:Focal Adhesion Kinase 2; D019950:Mitogen-Activated Protein Kinase 1
keywords: Cell function; Gax; IGF-1; Perivascular adipocyte; Signal transduction