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  • Sonic hedgehog signalling as a potential endobronchial biomarker in COPD.

Sonic hedgehog signalling as a potential endobronchial biomarker in COPD.

Respiratory research (2020-08-10)
Julien Ancel, Randa Belgacemi, Jeanne-Marie Perotin, Zania Diabasana, Sandra Dury, Maxime Dewolf, Arnaud Bonnomet, Nathalie Lalun, Philippe Birembaut, Myriam Polette, Gaëtan Deslée, Valérian Dormoy
ABSTRACT

The hedgehog (HH) pathway has been associated with chronic obstructive pulmonary disease (COPD) in genome-wide association studies and recent studies suggest that HH signalling could be altered in COPD. We therefore used minimally invasive endobronchial procedures to assess activation of the HH pathway including the main transcription factor, Gli2, and the ligand, Sonic HH (Shh). Thirty non-COPD patients and 28 COPD patients were included. Bronchial brushings, bronchoalveolar lavage fluid (BALF) and bronchial biopsies were obtained from fiberoptic bronchoscopy. Characterization of cell populations and subcellular localization were evaluated by immunostaining. ELISA and RNAseq analysis were performed to identify Shh proteins in BAL and transcripts on lung tissues from non-COPD and COPD patients with validation in an external and independent cohort. Compared to non-COPD patients, COPD patients exhibited a larger proportion of basal cells in bronchial brushings (26 ± 11% vs 13 ± 6%; p < 0.0001). Airway basal cells of COPD subjects presented less intense nuclear staining for Gli2 in bronchial brushings and biopsies (p < 0.05). Bronchial BALF from COPD patients contained lower Shh concentrations than non-COPD BALF (12.5 vs 40.9 pg/mL; p = 0.002); SHH transcripts were also reduced in COPD lungs in the validation cohort (p = 0.0001). This study demonstrates the feasibility of assessing HH pathway activation in respiratory samples collected by bronchoscopy and identifies impaired bronchial epithelial HH signalling in COPD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-HHIP antibody produced in mouse, clone 5D11, purified immunoglobulin, buffered aqueous solution
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Anti-GLI2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody
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Anti-GLI1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody
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Monoclonal Anti-Tubulin, Acetylated antibody produced in mouse, clone 6-11B-1, ascites fluid