Chemerin Regulated By Notch1 Affects Adipogenic Differentiation Of ADSCs And ADSCs-assisted Lipotransfer

Soft tissue defection caused by tumor resection or infection is the challenging area in reconstruction surgery.Although the synthetic materials can be used for filling defect or reconstruction of irregular defection,they need to face the allograft rejection or material differences of human body.In contrast,autologous tissue reconstruction has obvious advantages to synthetic materials.Among autologous tissues,adipose tissue has become a relatively ideal material for soft tissue repairation and reconstruction.The advantages of the tissue base as a rich source of adipose stem cell endothelial progenitor cells and hematopoietic progenitor cells make it a relatively ideal material for soft tissue repairation and reconstruction.Therefore,it is more and more common to use autologous fat transplantation to restore lost volume or repair large tissue defects.In particular,the repairation and reconstruction effect of application of liposuction to obtain a large amount of free fat for autologous transplantation is more effective and reliable.However,the absorption rate of graft fat after fat transplantation is difficult to predict,and it has been reported that the retention rate of graft fat can reach 10% to 90%,reducing the effectiveness of this method.Therefore,in order to improve the retention rate of graft fat,especially large-scale fat transplantation,a variety of methods and mechanisms have been studied to address this problem.The Notch signaling pathway is universally known to be a highly conserved pathway,and unlike other signaling pathways,Notch signaling pathway occurs in the process of cell-to-cell contaction.This signal transduction is initiated by the transmembrane receptors binding transmembrane ligands between parallel cells which mainly mediating the near-protein signaling pathway.Notch signaling pathway participate in the development and tissue renewal of various metazoans controlled by the process of cell proliferation,differentiation and apoptosis of cell fate.It is one of the core pathways in the process of cell proliferation,differentiation and apoptosis controling.In adults,Notch signaling is involved in the stem cell niches maintenance and stem cell differentiation to specific lineages.It is essential for stem cell homeostasis and tissue/organ development which rely on proliferation,lifespan prolongating,characteristics maintaining and preventing senescence of stem cells.Chemerin,to be a novel adipokines discoveried in 2007,has been identified as a protein factor possess autocrine paracrine and endocrine effects involved in immune inflammatory tumor development,adipogenesis,angiogenesis and energy metabolism in vivo.In stem cell studies,chemerin inhibits Wnt/ β-cateninin and notch signaling pathway which realted to osteogenic differentiation and promote lipid differentiation of bone marrow mesenchymal stem cells by activating the cmklr1 receptor.Therefore,chemerin/ cmklr1 signaling pathway can be used as a target gene for regulating lipid and osteogenic differentiation of MSCs.However,there was no study on the changes of chemerin expression during adipogenic differentiation of ADSCs and the correlation between chemerin / cmklr1 and notch1 signaling pathway.Objective: In order to find the potential factors of how to improve the retention rate of transplanted fat,the relationship between chemerin and notch1 in the process of adipogenic differentiation and regeneration of transplanted fat was explored.So as to explore the potential factors and lay a foundation for further research.Method: 1.The changes of chemerin expression during adipogenic differentiation of ADSCs were investigated at the cellular level,and the expression changes of chemerin in adipogenic differentiation of ADSCs were explored in vivo to verify whether chemerin could regulated ADSCs on the survival rate of transplanted adipocytes in CAL.2 To predicted the association between chemerin、cmklr1 and notch1 through bioinformatics analysis.3Futter exolore the role of notch1 in regulation of chemerin on adipogenic differentiation of ADSC and CAL in vivo and vitro base on the bioinformatics analysis.Result: 1 The expression of chemerin increased with adipogenic differentiation and maturation of ADSCs;The adipogenic differentiation of ADSCs regulated by chemerin was different,and the result of lipid differentiation formed by chemerin overexpression was the best in vivo experiment.Chemerin regulated ADSCs affected the survival rate of transplanted fat during cell-assisted fat transplantation,and the fat in the chemerin overexpression group presented the best survived rate.2 The interaction between chemerin and notch1 was verified by bioinformatics analysis.3 Overexpression of notch1 could reverse the effect of chemerin on promoting adipogenic differentiation of ADSCs and ADSCs assisting fat transplantation.Conclusion: Chemerin,as a functional protein secreted by ADSCs,is regulated by notch1 and affects the adipogenic differentiation of ADSCs and the fat survival rate of ADSCs-assisted fat transplantation.