Relationship:944

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Key Event Relationship Overview

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Description of Relationship

Upstream Event Downstream Event/Outcome
Proliferation of goblet cells, Increase Hyperplasia of goblet cells, Increase

AOPs Referencing Relationship

AOP Name Type of Relationship Weight of Evidence Quantitative Understanding
EGFR Activation Leading to Decreased Lung Function Directly Leads to Strong Weak

Taxonomic Applicability

Name Scientific Name Evidence Links
human Homo sapiens Strong NCBI
mouse Mus musculus Strong NCBI
rat Rattus norvegicus Strong NCBI

How Does This Key Event Relationship Work

Goblet cell hyperplasia arises from increased goblet cell proliferation resulting in enlargement of the tissue.

Weight of Evidence

Biological Plausibility

Hyperplasia is increased cell production in a normal tissue or organ, therefore, goblet cell hyperplasia is an increase in the number of goblet cells.

Empirical Support for Linkage

Include consideration of temporal concordance here

There is no empirical support as the KEs are equivalent in definition but on different levels of biological organization. Studies often study either the cellular or the tissue level but not the overlap.

Uncertainties or Inconsistencies

Quantitative Understanding of the Linkage

Is it known how much change in the first event is needed to impact the second? Are there known modulators of the response-response relationships? Are there models or extrapolation approaches that help describe those relationships?

As the definition of hyperplasia is proliferation of cells on a tissue level, the impact is one-to-one.

Evidence Supporting Taxonomic Applicability

Goblet cells have been reported to proliferate in human, mouse and rat studies (Takeno et al., 1996), (Ichinose et al., 2006), (Camateros et al., 2007), (Shatos et al., 2003), (Duh et al., 2000).

References

1. Camateros, P., Tamaoka, M., Hassan, M., Marino, R., Moisan, J., Marion, D., Guiot, M.-C., Martin, J.G., and Radzioch, D. (2007). Chronic asthma-induced airway remodeling is prevented by toll-like receptor-7/8 ligand S28463. Am. J. Respir. Crit. Care Med. 175, 1241–1249.

2. Caramori, G., Casolari, P., Di Gregorio, C., Saetta, M., Baraldo, S., Boschetto, P., Ito, K., Fabbri, L., Barnes, P., Adcock, I., et al. (2009). MUC5AC expression is increased in bronchial submucosal glands of stable COPD patients. Histopathology 55, 321–331.

3. Duh, G., Mouri, N., Warburton, D., and Thomas, D.W. (2000). EGF regulates early embryonic mouse gut development in chemically defined organ culture. Pediatr. Res. 48, 794–802.

4. Harkema, J., and Hotchkiss, J. (1993). Ozone- and endotoxin-induced mucous cell metaplasias in rat airway epithelium: novel animal models to study toxicant-induced epithelial transformation in airways. Toxicol Lett 68, 251–263.

5. Ichinose, T., Sadakane, K., Takano, H., Yanagisawa, R., Nishikawa, M., Mori, I., Kawazato, H., Yasuda, A., Hiyoshi, K., and Shibamoto, T. (2006). Enhancement of mite allergen-induced eosinophil infiltration in the murine airway and local cytokine/chemokine expression by Asian sand dust. J. Toxicol. Environ. Health A 69, 1571–1585.

6. Ma, R., Wang, Y., Cheng, G., Zhang, H., Wan, H., and Huang, S. (2005). MUC5AC expression up-regulation goblet cell hyperplasia in the airway of patients with chronic obstructive pulmonary disease. Chin Med Sci J 20, 181–184.

7. Mebratu, Y., Schwalm, K., Smith, K., Schuyler, M., and Tesfaigzi, Y. (2011). Cigarette smoke suppresses Bik to cause epithelial cell hyperplasia and mucous cell metaplasia. Am J Respir Crit Care Med 183, 1531–1538.

8. 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.

9. Shatos, M.A., Ríos, J.D., Horikawa, Y., Hodges, R.R., Chang, E.L., Bernardino, C.R., Rubin, P.A.D., and Dartt, D.A. (2003). Isolation and characterization of cultured human conjunctival goblet cells. Invest. Ophthalmol. Vis. Sci. 44, 2477–2486.

10. Takeno, S., Hamamura, N., Tatsukawa, T., and Yazin, K. (1996). [Proliferating cell nuclear antigen (PCNA) immunolocalization in human nasal epithelium with chronic sinusitis detected by confocal laser scanning microscopy]. Nihon Jibiinkoka Gakkai Kaiho 99, 1119–1125.