Sonic hedgehog signalling as a potential endobronchial biomarker in COPD

Area of Science:

• Pulmonary Medicine
• Molecular Biology
• Cell Biology

Background:

• The hedgehog (HH) pathway is implicated in chronic obstructive pulmonary disease (COPD) pathogenesis.
• Previous studies suggest alterations in HH signaling in COPD patients.
• This study investigates HH pathway activation in COPD using minimally invasive techniques.

Purpose of the Study:

• To assess the activation of the HH pathway in COPD.
• To evaluate the expression of HH pathway components, including Gli2 and Sonic HH (Shh).
• To determine the feasibility of using endobronchial procedures for HH pathway assessment.

Main Methods:

• Recruited 30 non-COPD and 28 COPD patients.
• Collected bronchial brushings, bronchoalveolar lavage fluid (BALF), and biopsies via fiberoptic bronchoscopy.
• Analyzed cell populations, protein localization, Shh protein levels (ELISA), and SHH transcripts (RNAseq).

Main Results:

• COPD patients had a higher proportion of basal cells in bronchial brushings.
• Reduced nuclear Gli2 staining was observed in airway basal cells of COPD subjects.
• Lower Shh concentrations in BALF and reduced SHH transcripts in lung tissue were found in COPD patients.

Conclusions:

• Endobronchial procedures are feasible for assessing HH pathway activation in respiratory samples.
• Bronchial epithelial HH signaling is impaired in COPD.
• Findings suggest a potential role for the HH pathway in COPD pathophysiology.