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Goblet cell hyperplasia leads to Hypersecretion, Mucus
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
Increased proliferation of goblet cells leads to hyperplasia of epithelial tissue, resulting in an increased amount of mucin produced by the proliferating goblet cells. Increased mucus results in mucus hypersecretion, narrowing of airways and difficulty breathing (Nadel, 2013). Smokers have an increased number of goblet cells in peripheral airways which is negatively correlated with low FEV1/FVC (lung function) which could be caused by mucus hypersecretion (Saetta et al., 2000).
Evidence Supporting this KER
An increased number of goblet cells in hyperplastic tissue can lead to mucus hypersecretion. Several studies show a correlation of hyperplasia and hypersecretion in rats in response to SO2 inhalation (Xu et al., 2000) and tobacco smoke (Coles et al., 1979). However, in these studies it was not confirmed that hyperplasia resulted from increased proliferation of goblet cells and hypersecretion could have been caused by goblet cell metaplasia. Studies have found low mitotic rates along with increased numbers of goblet cells in airways, suggesting differentiation into and not proliferation of goblet cells is occurring (Shimizu et al., 1996; Lamb and Reid, 1968).
Uncertainties and Inconsistencies
It may be more likely metaplasia is more dominant than hyperplasia in response to endotoxin and sulfur dioxide, as studies have found low mitotic rates along with increased number of goblet cells, suggesting differentiation into goblet cells is occurring (Shimizu et al., 1996), (Lamb and Reid, 1968).
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Many studies have shown hyperplasia and mucus hypersecretion in human, mouse and rat. Studies show a correlative relationship rather than a causal one, and sometimes these terms are used synonymously.
1. Coles, S.J., Levine, L.R., and Reid, L. (1979). Hypersecretion of mucus glycoproteins in rat airways induced by tobacco smoke. Am. J. Pathol. 94, 459–471.
2. Lamb, D., and Reid, L. (1968). Mitotic rates, goblet cell increase and histochemical changes in mucus in rat bronchial epithelium during exposure to sulphur dioxide. J. Pathol. Bacteriol. 96, 97–111.
3. Nadel, J. (2013). Mucous hypersecretion and relationship to cough. Pulm Pharmacol Ther 26, 510–513.
4. Saetta, M., Turato, G., Baraldo, S., Zanin, A., Braccioni, F., Mapp, C., Maestrelli, P., Cavallesco, G., Papi, A., and Fabbri, L. (2000). Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation. Am J Respir Crit Care Med 161, 1016–1021.
5. Shimizu, T., Takahashi, Y., Kawaguchi, S., and Sakakura, Y. (1996). Hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium induced by endotoxin. Am. J. Respir. Crit. Care Med. 153, 1412–1418.
6. Xu, J., Zhao, M., and Liao, S. (2000). Establishment and pathological study of models of chronic obstructive pulmonary disease by SO2 inhalation method. Chin Med J Engl 113, 213–216.