title: Activation of Wnt3a signaling stimulates intestinal epithelial repair by promoting c-Myc-regulated gene expression.
abstract: In response to mucosal injury, epithelial cells modify the patterns of expressed genes to repair damaged tissue rapidly. Our previous studies have demonstrated that the transcription factor c-Myc is necessary for stimulation of epithelial cell renewal during mucosal healing, but the up-stream signaling initiating c-Myc gene expression after injury remains unknown. Wnts are cysteine-rich glycoproteins that act as short-range ligands to locally activate receptor-mediated signaling pathways and correlate with the increased expression of the c-Myc gene. The current study tested the hypothesis that Wnt3a signaling is implicated in intestinal epithelial repair after wounding by stimulating c-Myc expression. Elevated Wnt3a signaling in intestinal epithelial cells (IEC-6 line) by coculturing with stable Wnt3a-transfected fibroblasts or ectopic overexpression of the Wnt3a gene enhanced intestinal epithelial repair after wounding. This stimulatory effect on epithelial repair was prevented by silencing the Wnt coreceptor LRP6 or by c-Myc silencing. Activation of the Wnt3a signaling pathway increased β-catenin nuclear translocation by decreasing its phosphorylation and stimulated c-Myc expression during epithelial repair after wounding. In stable Wnt3a-transfected IEC-6 cells, increased levels of c-Myc were associated with an increase in expression of c-Myc-regulated genes cyclcin D1 and cyclin E, whereas c-Myc silencing inhibited expression of cyclin D1 and cyclin E and delayed epithelial repair. These results indicate that elevated Wnt3a signaling in intestinal epithelial cells after wounding stimulates epithelial repair by promoting c-Myc-regulated gene expression.
authors: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: Lan
authors: L
authors: Liu
authors: Jaladanki N
authors: JN
authors: Rao
authors: Tongtong
authors: T
authors: Zou
authors: Lan
authors: L
authors: Xiao
authors: Alexis
authors: A
authors: Smith
authors: Ran
authors: R
authors: Zhuang
authors: Douglas J
authors: DJ
authors: Turner
authors: Jian-Ying
authors: JY
authors: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*; D060509:Wnt3A Protein / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics*
chemical_list: C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse