The control of C/EBPbeta DNA-binding affinity by retinoic acid and Smad3 during mesenchymal stem cell differentiation

点击翻译按钮获取中文摘要

Cells that make up fat, bone cartilage and muscle, can be generated from a single stem cell called a mesenchymal stem cell. Research has shown that vitamin A can prevent to formation of new fat cells and can help produce more bone cells. We have shown that vitamin A can act, at a molecular level, through a protein called C/EBPbeta. C/EBPbeta's role is to use DNA to make new proteins required to convert stem cells into mature bone or fat cells. We have discovered that another protein, Smad3, is expressed at higher levels in stem cells treated with vitamin A, and we believe this protein is involved in preventing C/EBPbeta from interacting with DNA, something it needs to do to be active. This proposal aims to understand how vitamin A blocks fat cell formation and enhances bone cell production through Smad3 interference with C/EBPbeta activity. We will (1) assess Smad3 interference of C/EBPbeta activity during fat cell and bone cell formation; (2) Characterize how Smad3 and C/EBPbeta interact in the cell and finally (3) identify new genes that are regulated by this process. The results of this work will help us better understand how vitamin A controls cell functions and how mesenchymal stem cell maturation is regulated - in essence providing invaluable information about how fat and bone cells are formed in the body.