N-acetylcysteine inhibits gene and protein expression of MUC5AC in COPD-relevant human models: evidence from a meta-analysis.

Authors

Luigino Calzetta, Shima Gholamalishahi, Gian Marco Manzetti, Elena Pistocchini, Paola Rogliani

Published in

European journal of pharmacology. Pages 179437. Oct 14, 2026. Epub Oct 14, 2026.

Abstract

Chronic mucus hypersecretion is highly prevalent in chronic obstructive pulmonary disease and is associated with worse outcomes. MUC5AC is a key inducible gel-forming mucin driving pathological mucus overproduction. N-acetylcysteine (NAC) is widely used as a mucolytic and exhibits antioxidant and anti-inflammatory properties. Its quantitative impact on MUC5AC regulation has not been formally synthesized. We performed a systematic review and meta-analysis (OSF registration ID: 2vym4) of original studies evaluating the effect of NAC on MUC5AC gene and protein expression in human respiratory cell models of mucus hypersecretion. Standardized mean differences with 95% CIs were pooled using DerSimonian-Laird random-effects models. Heterogeneity, publication bias, sensitivity analyses, and random-effects meta-regression on NAC dose were conducted. Fifteen articles were included. NAC significantly reduced MUC5AC mRNA (standardized mean difference -1.30, 95% CI: -1.61 to -0.98; I²=37.07%), without significant dose-response. NAC produced very large reductions in extracellular (-2.70, 95% CI: -3.29 to -2.11; I²=48.89%) and intracellular (-2.38, 95% CI: -3.27 to -1.48; I²=67.35%) MUC5AC protein, with significant dose-response relationships for both. After sensitivity analyses, the pooled protein effect remained very large (-2.00, 95% CI: -2.38 to -1.62; I²=25.63%). Funnel plots and Egger's tests suggested publication bias, which diminished after exclusion of influential comparisons. NAC robustly inhibits MUC5AC gene and protein expression in human pre-clinical models of mucus hypersecretion, supporting a strong mucoregulatory action that complements mucolytic and antioxidant effects. These data reinforce the rationale for NAC use in chronic obstructive pulmonary disease patients with a hypersecretory phenotype.

PMID:
42874904
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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