Nuclear β-catenin is increased in systemic sclerosis pulmonary fibrosis and promotes lung fibroblast migration and proliferation

Anna P. Lam*, Annette S. Flozak, Susan Russell, Jun Wei, Manu Jain, Gökhan M. Mutlu, G. R.Scott Budinger, Carol A. Feghali-Bostwick, John Varga, Cara J. Gottardi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Pulmonary fibrosis is a disease that results in loss of normal lung architecture, but the signaling events that drive tissue destruction are incompletely understood. Wnt/β-catenin signaling is important in normal lung development, but whether abnormal signaling occurs in lung fibrosisdueto systemic sclerosis and the consequences of β-catenin signaling toward the fibrogenic phenotyperemain poorly defined. In this study, we show nuclear β-catenin accumulation in fibroblastic foci from lungs of patients with systemic sclerosis - associated advanced pulmonary fibrosis. Forced activation of β-catenin signaling in three independently derived sources of normal human lung fibroblasts promotes proliferation and migratory activities but is not sufficient to activate classic markers of fibroblast activation, such as TGF-β, type 1 collagen, α-smooth muscle actin, and connective tissue growth factor. These findings indicate that activation of β-catenin signaling in pulmonary fibroblasts may be a common feature of lung fibrosis, contributing to fibroproliferative and migratory activities associated with the disease.

Original languageEnglish (US)
Pages (from-to)915-922
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number5
DOIs
StatePublished - Nov 1 2011

Keywords

  • Fibrosis
  • Scleroderma
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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