Authors: Yongho Lee Soo Hyun Kim Yoo Jeong Lee Eun Seok Kang ByungWan Lee Bong Soo Cha Jae Woo Kim Dae Hyun Song Hyun Chul Lee
Publish Date: 2013/05/21
Volume: 70, Issue: 20, Pages: 3959-3971
Abstract
Snail belongs to the superfamily of zincfinger transcription factors and plays a crucial role in processes regulating cell fate such as the formation of mesoderm and initiation of epithelial–mesenchymal transition We have previously discovered that Snail modulates adiponectin expression in 3T3L1 cells during adipogenesis In the present study we elucidated the functional role of Snail in adipocyte differentiation and its underlying molecular mechanism Snail expression was dramatically decreased during adipogenesis in 3T3L1 cells Overexpression of Snail blocked adipocyte differentiation by suppressing the expression of peroxisome proliferatoractivated receptor gamma PPARγ and CCAATenhancerbinding protein alpha while knockdown of Snail expression stimulated adipogenesis in 3T3L1 cells Chromatin immunoprecipitation assay and luciferase assay showed that Snail inhibits the transcriptional activity of the PPARγ gene by directly binding to the Ebox motifs in the PPARγ promoter Wnt10b induced phosphorylation of glycogen synthase kinase 3 beta GSK3β leading to inhibition of adipogenesis in 3T3L1 cells in accordance with increased expression of Snail whereas adipogenic capacity was restored in Snail siRNAtransfected preadipocytes LiCl a GSK3β inhibitortreated cells also showed increased expression of Snail with a reduced adipogenic potential Snailoverexpressing 3T3F442A cells did not differentiate into mature adipocytes in immunodeficient nude mice Taken together Snail is a novel regulator of adipocyte differentiation which acts by direct suppression of PPARγ expression Our data also indicate that the expression of Snail is mediated by the Wnt–GSK3β signaling pathwayWe sincerely thank Chun Sik Park MD PhD for his critical comments on the study This study was supported by a faculty research grant of Yonsei University College of Medicine for 2012 620122010Y L S H K and Y J L researched data Y L S H K and H C L wrote the manuscript E S K B–W L B S C J W K and D H S contributed to the discussion and reviewed and edited the manuscript H C L is the guarantor of this work and had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis
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