Gax suppresses chemerin/CMKLR1-induced preadipocyte biofunctions through the inhibition of Akt/mTOR and ERK signaling pathways.
Adipose tissue is closely associated with angiogenesis and vascular remodeling. Chemerin is involved in inflammatory reaction and vascular dysfunction. However, the mechanisms of chemerin participating in vascular remodeling and whether Growth arrest-specific homeobox (Gax) can effectively intervene it remain obscured. Here, 3T3-F442A preadipocytes were cultured, injected into athymic mice to model fat pads, and treated respectively with Ad-chemerin, Ad-Gax, or specific inhibitors in vitro and in vivo. MTT, flow cytometry, Western blotting, and imunohisto(cyto)-chemistry analyses showed that chemerin enhanced the expression of FABP4 and VEGF, activated Akt/mTOR and ERK pathways, increased the cell percent of S phase, decreased the percent of G0-G1 phase and apoptotic cells, and augmented neovascular density in fat pads. Inversely, Gax suppressed the expression of these adipogenic and vasifactive markers and these signaling proteins, decreased the percent of S phase cells, and increased those of G0-G1 phase and apoptotic cells, and reduced the neovascular density. Our results indicate that chemerin-CMKLR1 activates Akt/mTOR and ERK pathways and facilitates preadipocyte proliferation, adipogenesis, and angiogenesis. Contrarily, Gax weakens the effect of chemerin on preadipocyte biofunctions.
Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong, China.
Yunqi
Y
Jiang
Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong, China.
Ping
http://orcid.org/0000-0002-3039-5985
P
Liu
College of Pharmacy, Shandong University, Jinan, Shandong, China.
Wenlin
W
Jiao
Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong, China.
Juan
J
Meng
Central Laboratory, The Qilu Hospital of Shandong University, Jinan, Shandong, China.
Jinbo
J
Feng
D016475:3T3 Cells; D017667:Adipocytes / Q000201:enzymology* / Q000637:transplantation; D050156:Adipogenesis; D000273:Adipose Tissue / Q000098:blood supply / Q000201:enzymology*; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
C486456:CMKLR1 protein, mouse; D018925:Chemokines; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C484194:Meox2 protein, mouse; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D042461:Vascular Endothelial Growth Factor A; C523686:chemerin protein, mouse; C467480:vascular endothelial growth factor A, mouse; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
Gax; adipogenesis; angiogenesis; chemerin; preadipocyte