CCAAT/enhancer-binding proteins(C/EBPs)are a family of at least six identified transcription factors that contain a highly conserved basic leucine zipper domain and interact selectively with duplex DNA to regulate target gene expression.C/EBPs play important roles in various physiological processes,and their abnormal function can lead to various diseases.Recently,accumulating evidence has demonstrated that aberrant C/EBP expression or activity is closely associated with the onset and progression of fibrosis in several organs and tissues.During fibrosis,various C/EBPs can exert distinct functions in the same organ,while the same C/EBP can exert distinct functions in different organs.Modulating C/EBP expression or activity could regulate various molecular processes to alleviate fibrosis in multiple organs;therefore,novel C/EBPs-based therapeutic methods for treating fibrosis have attracted considerable attention.In this review,we will explore the features of C/EBPs and their critical functions in fibrosis in order to highlight new avenues for the development of novel therapies targeting C/EBPs.
Epiboly,the coordinated spreading of the enveloping layer(EVL),the yolk syncytial layer(YSL)and the deep cells(DCs)toward the vegetal pole,is required for gastrulation.Interference with the EVL leads to early developmental failure.However,the genetic factors underlying EVL differentiation are so far unknown.By in-depth analyzing of single-cell sequencing data from 4 h post fertilization zebrafish embryos,we identified 105 genes(FDR<0.05)which showed highly specific EVL expression,among which the transcription factor cebpb and genes(krt18,cldne,cldnb,krt4,krt5)involved in cell-cell junction formation were exclusively expressed in EVL.To explore the role of cebpb in EVL differentiation,we knocked down its expression by morpholino-labeled antisense RNA.The morphant embryos showed disrupted EVL and developmental termination prior to epiboly.In accordance,expression of the EVL specific cell-adhesion molecule genes were significantly reduced.Thus,cebpb is the earliest EVL marker and essential for EVL differentiation in zebrafish.The elucidation of the specific EVL gene set provides us new insights into the molecular mechanisms underlying EVL differentiation.
