Disruption of β-catenin/CBP signaling inhibits human airway epithelial-mesenchymal transition and repair

The International Journal of Biochemistry & Cell Biology
Fatemeh MoheimaniDarryl A Knight

Abstract

The epithelium of asthmatics is characterized by reduced expression of E-cadherin and increased expression of the basal cell markers ck-5 and p63 that is indicative of a relatively undifferentiated repairing epithelium. This phenotype correlates with increased proliferation, compromised wound healing and an enhanced capacity to undergo epithelial-mesenchymal transition (EMT). The transcription factor β-catenin plays a vital role in epithelial cell differentiation and regeneration, depending on the co-factor recruited. Transcriptional programs driven by the β-catenin/CBP axis are critical for maintaining an undifferentiated and proliferative state, whereas the β-catenin/p300 axis is associated with cell differentiation. We hypothesized that disrupting the β-catenin/CBP signaling axis would promote epithelial differentiation and inhibit EMT. We treated monolayer cultures of human airway epithelial cells with TGFβ1 in the presence or absence of the selective small molecule ICG-001 to inhibit β-catenin/CBP signaling. We used western blots to assess expression of an EMT signature, CBP, p300, β-catenin, fibronectin and ITGβ1 and scratch wound assays to assess epithelial cell migration. Snai-1 and -2 expressions were determined using ...Continue Reading

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Citations

Sep 24, 2016·Respiratory Research·Fatemeh MoheimaniDarryl A Knight
Feb 1, 2017·BMC Pulmonary Medicine·Dorota StefanowiczTillie-Louise Hackett
May 28, 2020·Allergy·Irene H HeijinkMartijn C Nawijn
Oct 28, 2019·Physiological Reports·Jennifer A AguiarJeremy A Hirota
May 14, 2019·Expert Opinion on Therapeutic Targets·Gaetano CaramoriIan M Adcock
Jan 19, 2020·Chest·Darryl A KnightMichael Schuliga
Jan 26, 2016·Pharmacology & Therapeutics·Stephanie KaypeeTapas K Kundu

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