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Goblet cell metaplasia leads to Increase, Mucin production
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
Chronic mucus hypersecretion is a main feature of chronic lung diseases, and the presence of goblet cell hyperplasia or goblet cell metaplasia in the lungs of chronic obstructive pulmonary disease, asthma and cystic fibrosis patients has been inferred as cause for sustained mucus production (Rose and Voynow, 2006; Munkholm and Mortensen, 2014).
Evidence Supporting this KER
This KER is inferred: According to Rose and Voynow, “Secretory cell hyperplasia is a prerequisite for sustained mucus hypersecretion/mucin overproduction” (Rose and Voynow, 2006).
This KER is inferred. However, that an increase in goblet cell numbers also increases mucin production is highly plausible. Studies in human cells, mice and rats demonstrate that mucin content or MUC5AC mRNA and protein expression increase in the presence of histologically confirmed goblet cell metaplasia. However, because both events are measured in parallel and causal evidence is missing, our confidence is moderate.
Uncertainties and Inconsistencies
In some cases, it appears that the authors use the terms "goblet cell hyperplasia" and "goblet cell metaplasia" interchangeably, making the evaluation of the available evidence difficult. Because goblet cell metaplasia is also a feature of epithelial cell remodeling in the context of wound healing, its appearance can be transient. At least one study indicates that goblet cell hyperplasia is also found in healthy non-smokers (never- and former smokers), where it appears as isolated foci—as opposed to the more extensive involvement of the airway epithelium seen in e.g. COPD patients (Polosukhin et al., 2011).
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Munkholm, M., and Mortensen, J. (2014). Mucociliary clearance: pathophysiological aspects. Clin Physiol Funct Imaging 34, 171-177.
Polosukhin, V.V., Cates, J.M., Lawson, W.E., Milstone, A.P., Matafonov, A.G., Massion, P.P., et al. (2011). Hypoxia‐inducible factor‐1 signalling promotes goblet cell hyperplasia in airway epithelium. J Pathol 224, 203-211.
Rose, M.C., and Voynow, J.A. (2006). Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev 86, 245-278.