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Telomerase Reverse Transcriptase Enzyme (hTERT) expression in bronchial mucosa inversely correlates with the severity of airway obstruction in patients with chronic airway obstructive diseases

Moermans, C.; Medard, L.; Graff, S.; Bougard, N.; Schleich, F.; GUIOT, J.; Corhay, J.-L.; Louis, R.

2022-12-09 respiratory medicine
10.1101/2022.12.08.22283249 medRxiv
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RationaleAsthma and Chronic Obstructive Pulmonary Disease (COPD) are the two main chronic airway inflammatory diseases related to aging. Cellular aging is prevented by telomeres and their shortening induces cellular senescence. Human Telomerase Reverse Transcriptase Enzyme (hTERT) can act directly on DNA and prevent telomere shortening. The goal of this study was to assess hTERT expression in the bronchial mucosa of patients suffering from chronic airway obstructive diseases and to relate the hTERT expression to demographics and lung function characteristics. MethodsWe collected bronchial biopsies from 38 patients suffering from chronic airway diseases including 21 severe asthmatics and 17 COPD who underwent bronchoscopy in routine practice. hTERT expression was assessed by immunochemistry and co-immunostaining was performed to identify hTERT positive cells within the different immune cell populations. ResultshTERT expression in airway mucosa was essentially found in structural cells. Among leukocytes, lymphocytes were the principal cells expressing hTERT. On the whole cohort, hTERT expression score was not different between men and women and not influenced by the age nor by the smoking history as reflected by the pack years. Total airway hTERT positive staining score positively correlated with post-bronchodilation (post-BD) FEV1 % predicted and FEV1/FVC. (r=0.38, p<0.05 for both). hTERT+ lymphocytes were also positively correlated to post-BD FEV1/FVC (r=0.37, p<0.05). Consequently, hTERT expression was lower in those patients with fixed airway obstruction (post-BD FEV1/FVC < 70%). There was no difference between asthmatics and COPD. ConclusionsIn patients with chronic airway diseases, total and lymphocyte hTERT expressions inversely correlate with the degree of airway obstruction and are reduced in patients with fixed airway obstruction, which supports a role of hTERT in airway remodeling.

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