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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: 3T3-L1 Cells, Adipocytes, Adipogenesis, Animals, Cell Communication, Cell Proliferation, Connexin 43, Gap Junctions, Glycyrrhetinic Acid, Male, Mice, Mice, Inbred C57BL, Mitosis, RNA, Small Interfering.
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Is gap-junctional communication required for mitotic clonal expansion during adipogenesis? Context: Gap-junctional communication (GJC) plays critical roles in cell growth and differentiation. Several studies have demonstrated the involvement of GJC in myogenesis and osteogenesis; however, the role of GJC in adipogenesis has not been fully studied. Thus, we investigated the role of GJC in adipogenesis. 3T3-L1 preadipocytes were differentiated in the presence of gap junction inhibitor, 18-alpha-glycyrrhetinic acid (AGA), and accumulation of cytoplasmic triglycerides was measured. 3T3-L1 cells were transfected with 100 nM small interfering RNA duplexes targeting connexin (Cx) 43. The mRNA levels of CCAAT/enhancer-binding protein (C/EBP) alpha, peroxisome proliferator-activated receptor gamma, glucose transporter 4, C/EBPbeta, and Cx43 were measured by real-time polymerase chain reaction. The protein levels of C/EBPbeta were quantitated by Western blotting. The cell proliferation was measured by counting cell numbers, and DNA synthesis was measured by bromodeoxyuridine incorporation. AGA inhibited adipocyte differentiation dose-dependently. The lipid accumulation and the mRNA levels of C/EBPalpha, peroxisome proliferator-activated receptor gamma, and glucose transporter 4 were markedly reduced in AGA-treated adipocytes. The mRNA levels of C/EBPbeta did not decrease; however, C/EBPbeta [liver-enriched transcriptional activator protein (LAP)] expression and the C/EBPbeta (LAP)-to-C/EBP [liver-enriched transcriptional inhibitory protein (LIP)] ratio were reduced by AGA treatment. The increase in both cell number and DNA synthesis, which occurs during mitotic clonal expansion, was reduced by AGA in a dose-dependent fashion. The major component of gap junctions in 3T3-L1 cells was Cx43. Down-regulation of Cx43 using small interfering RNA reduced the expression of C/EBPbeta (LAP) and inhibited adipogenesis.
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Our data suggest that GJC plays some important roles in adipogenesis through inhibiting mitotic clonal expansion and modulating C/EBPbeta (LAP) expression. Final Decision: yes