title: Nuclear β-catenin is increased in systemic sclerosis pulmonary fibrosis and promotes lung fibroblast migration and proliferation.
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 fibrosis due to systemic sclerosis and the consequences of β-catenin signaling toward the fibrogenic phenotype remain 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.
authors: Department of Medicine, Division of Pulmonary and Critical Care, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. a-lam4@northwestern.edu
authors: Anna P
authors: AP
authors: Lam
authors: Annette S
authors: AS
authors: Flozak
authors: Susan
authors: S
authors: Russell
authors: Jun
authors: J
authors: Wei
authors: Manu
authors: M
authors: Jain
authors: Gökhan M
authors: GM
authors: Mutlu
authors: G R Scott
authors: GR
authors: Budinger
authors: Carol A
authors: CA
authors: Feghali-Bostwick
authors: John
authors: J
authors: Varga
authors: Cara J
authors: CJ
authors: Gottardi
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000378:metabolism*; D015398:Signal Transduction; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: D051176:beta Catenin