Related Experiment Video
Updated: Dec 18, 2025

Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study
Published on: April 11, 2018
Defective BACH1/HO-1 regulatory circuits in cystic fibrosis bronchial epithelial cells
Shashipavan Chillappagari1, Virajith Garapati2, Poornima Mahavadi2
1Institute of Biochemistry, Justus-Liebig-University, D-35392, Giessen, Germany; Department of Internal Medicine, Justus-Liebig University, Giessen, Germany; University of Giessen and Marburg Lung Center (UGMLC), Member of the German Centre for Lung Research (DZL), Giessen, Germany.
Background:
The stress-regulated enzyme hemeoxygenase-1 (HO-1) contributes to the cell response towards inflammation and oxidative stress. We previously reported on curtailed HO-1 expression in cystic fibrosis (CF) bronchial epithelial (CFBE41o-) cells and CF-mice, but the molecular mechanisms for this are not known. Here, we compared healthy and CF bronchial epithelial cells for regulatory circuits controlling HO-1 protein levels.
Methods:
In this study, we employed immunohistochemistry on CF and healthy lung sections to examine the BACH1 protein expression. Alteration of BACH1 protein levels in 16HBE14o- and CFBE41o- cells was achieved by using either siRNA-mediated knockdown of BACH1 or by increasing miRNA-155 levels. HO-1 luciferase reporter assay was chosen to examine the downstream affects after BACH1 modulation.
Results:
Human CF lungs and cells showed increased levels of the HO-1 transcriptional repressor, BACH1, and increased miR-155 expression. Knockdown studies using BACH1 siRNA and overexpression of miR-155 did not significantly rescue HO-1 expression in CFBE41o- cells. Elevated BACH1 expression detected in CF cells was refractory to the inhibitory function of miR-155 and was instead due to increased protein stability.
Conclusion:
We observed defects in the inhibitory activities of miR-155 and BACH1 on HO-1 expression in CF cells. Thus various defective regulatory loops account for dysregulated BACH1 expression in CF, which in turn may contribute to low HO-1 levels.
Related Concept Videos
Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
Cystic Fibrosis: Management
Sinus disease and chronic...
GPCRs Regulate Adenylyl Cylase Activity
Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation
Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

