title: Involvement of IGF-1 and MEOX2 in PI3K/Akt1/2 and ERK1/2 pathways mediated proliferation and differentiation of perivascular adipocytes.
abstract: Perivascular adipocyte (PVAC) proliferation and differentiation were closely involved in cardiovascular disease. We aimed to investigate whether phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways enhance PVAC functions activated by insulin-like growth factor 1(IGF-1) and suppressed by mesenchyme homeobox 2 (MEOX2). In this study, PVACs from primary culture were cultured and induced to differentiate. Cell viability assays demonstrated that IGF-1 promoted PVAC proliferation and differentiation. However MEOX2 counteracted these IGF-1-mediated actions. Flow Cytometry revealed that IGF-1 increased S phase cells and decreased apoptosis; however, MEOX2 decreased S phase cells, increased G0-G1 phase cells, and promoted apoptosis. During PVAC proliferation and differentiation, IGF-1 activated PI3K/Akt1/2 and ERK1/2 signaling pathways, upregulated the expression of these signaling proteins and FAS, and increased PVAC lipid content. In contrast, MEOX2 constrained the phosphorylation of ERK1/2 and Akt1/2 protein, down-regulated these signaling molecules and FAS, and decreased PVAC lipid content. Instead, MEOX2 knockdown enhanced the ERK1/2 and Akt1/2 phosphorylation, augmented the expression of these signaling molecules and FAS, and increased PVAC lipid content. Our findings suggested that PI3K/Akt1/2 and ERK1/2 activation mediated by IGF-1 is essential for PVAC proliferation and differentiation, and MEOX2 is a promising therapeutic gene to intervene in the signaling pathways and inhibit PVAC functions.
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, No. 247, Beiyuan Road, Shandong, Jinan 250033, China. Electronic address: lping@sdu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Central Laboratory, The Second Hospital of Shandong University, Shandong, Jinan 250033, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Kong
authors.affiliation: Central Laboratory, The Second Hospital of Shandong University, Shandong, Jinan 250033, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, No. 247, Beiyuan Road, Shandong, Jinan 250033, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Wendeng Central Hospital of Weihai City, Shandong, Weihai 264400, China.
authors.forename: Haijia
authors.initials: H
authors.lastname: Xu
authors.affiliation: Central Laboratory, The Second Hospital of Shandong University, Shandong, Jinan 250033, China.
authors.forename: Tonggang
authors.initials: T
authors.lastname: Qi
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, No. 247, Beiyuan Road, Shandong, Jinan 250033, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Meng
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D064429:Fatty Acid Synthases / Q000378:metabolism; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008055:Lipids / Q000032:analysis; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D064429:Fatty Acid Synthases; D018398:Homeodomain Proteins; D007334:Insulin-Like Growth Factor I; D008055:Lipids; D020928:Mitogen-Activated Protein Kinases; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C081336:Meox2 protein, rat; C494920:Akt1 protein, rat; C494923:Akt2 protein, rat
keywords: Cell function; IGF-1; MEOX2; Perivascular adipocyte; Signaling pathway