title: β-catenin signaling:  a novel mediator of fibrosis and potential therapeutic target.
abstract: OBJECTIVE
  The Wnt/β-catenin signaling pathway plays a critical role in development and adult tissue homeostasis. Recent investigations implicate Wnt/β-catenin signaling in abnormal wound repair and fibrogenesis. The purpose of this review is to highlight recent key studies that support a role for Wnt/β-catenin signaling in fibrosis.
  
  
  RESULTS
  Studies of patients with fibrotic diseases have demonstrated changes in components of the Wnt/β-catenin pathway. In animal models, perturbations in Wnt/β-catenin signaling appear to aggravate or ameliorate markers of injury and fibrosis in a variety of different tissues. Studies also suggest that fibroblasts from different tissue sources may have markedly divergent responses to Wnt/β-catenin signaling. Cross-talk between Wnt/β-catenin and transforming growth factor-β pathways is complex and context-dependent, and may promote fibrogenesis through coregulation of fibrogenic gene targets. High throughput screening has identified several novel chemical inhibitors of Wnt/β-catenin signaling that may be of therapeutic potential.
  
  
  CONCLUSIONS
  Wnt/β-catenin signaling appears important in normal wound healing and its sustained activation is associated with fibrogenesis. The mechanism by which Wnt/β-catenin signaling may modify the response to injury is cell-type and context-dependent. Better understanding of this signaling pathway may provide a promising new therapeutic approach for human fibrotic diseases.
authors: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors: Anna P
authors: AP
authors: Lam
authors: Cara J
authors: CJ
authors: Gottardi
mesh_terms: D000818:Animals; D005355:Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008954:Models, Biological; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D060449:Wnt Signaling Pathway; D014945:Wound Healing / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*; D000099274:Frizzled-Related Proteins
chemical_list: D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D051176:beta Catenin; D000099274:Frizzled-Related Proteins; C495270:CTNNB1 protein, human