title: MEK/ERK signaling is involved in the role of VEGF and IGF1 in cardiomyocyte differentiation of mouse adipose tissue-derived stromal cells.
abstract: BACKGROUND
  We found that mouse brown adipose tissue-derived stromal cells (BATDCs), but not white adipose tissue-derived stromal cells (WATDCs), could spontaneously differentiate into cardiomyocyte-like cells in a simple culture medium. This study would find out some critical trophic factors that were responsible for such difference in differentiation, and further determine the involved signaling pathway.
  
  
  RESULTS
  The cardiomyocyte differentiation capacity of cells was identified by morphological observations, immunofluorescence staining, and evaluation of expression of cardiomyocyte specific markers. The amount of vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF1) secreted by cells was determined by ELISA analysis. Results indicated that BATDCs secreted higher levels of VEGF and IGF1 than WATDCs. Supplementation of BATDCs with antibodies against VEGF receptor Flt-1 or IGF1 receptor Igf-1rα significantly suppressed the cardiac differentiation capacity of the cells. Additionally, anti-Flt-1 and anti-Igf-1rα antibodies decreased phosphorylation of ERK1/2 in BATDCs. Inhibition of MEK/ERK activity by the inhibitor PD0325901 or by RNA interference blunted the cardiac differentiation of BATDCs. Loading recombinant VEGF and IGF1, or transfecting their expression vectors into WATDCs, promoted cardiac differentiation of the cells. Preincubation with PD0325901, before VEGF and IGF1 supplementation or vector transfections, blocked the stimulation of cardiac differentiation in WATDCs.
  
  
  CONCLUSIONS
  These findings indicated that VEGF and IGF1 were critical factors for the spontaneous cardiac differentiation of BATDCs, and MEK/ERK signaling was involved in the role of VEGF and IGF1. VEGF and IGF1 could be used to promote the development of cardiomyocyte phenotype in WATDCs.
authors.affiliation: College of Life Sciences, Shandong Agricultural University, Tai'an 271018, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Shandong Agricultural University, Tai'an 271018, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Shandong Agricultural University, Tai'an 271018, China.
authors.forename: Xianning
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Shandong Agricultural University, Tai'an 271018, China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Shandong Agricultural University, Tai'an 271018, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Shandong Agricultural University, Tai'an 271018, China. Electronic address: hfli1228@163.com.
authors.forename: Haifang
authors.initials: H
authors.lastname: Li
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D012313:RNA; D007334:Insulin-Like Growth Factor I; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases
keywords: Adipose tissue-derived stromal cells (ATDCs); Cardiomyocyte differentiation; Insulin-like growth factor 1 (IGF1); MEK/ERK signaling; Vascular endothelial growth factor (VEGF)