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Minireview: Pref-1: role in adipogenesis and mesenchymal cell fate Sul HSMol Endocrinol 2009[Nov]; 23 (11): 1717-25Preadipocyte factor-1 [Pref-1; also called Dlk1 (Delta-like protein 1)] is made as an epidermal growth factor-repeat containing transmembrane protein that produces a biologically active soluble form by TNF-alpha-converting enzyme (TACE)-mediated cleavage. Soluble Pref-1 activates the MAPK kinase/ERK pathway. In adipose tissue, Pref-1 is specifically expressed in preadipocytes but not in adipocytes and thus is used as a preadipocyte marker. Inhibition of adipogenesis by Pref-1 has been well established in vitro as well as in vivo by ablation and overexpression of Pref-1. SRY (sex determining region Y)-box 9 (Sox9), a transcription factor expressed in preadipocytes to suppress CCAAT enhancer binding protein beta and (C/EBP) delta expression, is required to be down-regulated before adipocyte differentiation can proceed. By activating MAPK kinase/ERK, Pref-1 prevents down-regulation of Sox9, resulting in inhibition of adipogenesis. Furthermore, by inducing Sox9, Pref-1 promotes chondrogenic induction of mesenchymal cells but prevents chondrocyte maturation as well as osteoblast differentiation. Thus, Pref-1 directs multipotent mesenchymal cells toward the chondrogenic lineage but inhibits differentiation into adipocytes as well as osteoblasts and chondrocytes. Pref-1, encoded by an imprinted gene, has also been detected in progenitor cells in various tissues during regeneration and therefore may have a more general role in maintaining cells in an undifferentiated state.|*Adipogenesis[MESH]|*Gene Expression Regulation, Developmental[MESH]|Adipocytes/*cytology[MESH]|Animals[MESH]|Calcium-Binding Proteins[MESH]|Cell Lineage[MESH]|Glucose/metabolism[MESH]|Humans[MESH]|Insulin/metabolism[MESH]|Intercellular Signaling Peptides and Proteins/metabolism/*physiology[MESH]|MAP Kinase Signaling System[MESH]|Membrane Proteins/metabolism/*physiology[MESH]|Mesoderm/*cytology[MESH]|Mice[MESH]|Protein Structure, Tertiary[MESH]|Stem Cells/cytology[MESH] |
