Event: 923

Key Event Title


Increase, Proliferation of goblet cells

Short name


Increase, Proliferation of goblet cells

Biological Context


Level of Biological Organization

Cell term


Organ term


Organ term

Key Event Components


Process Object Action
cell proliferation goblet cell increased

Key Event Overview

AOPs Including This Key Event


AOP Name Role of event in AOP
Decreased lung function KeyEvent



Taxonomic Applicability


Term Scientific Term Evidence Link
human Homo sapiens High NCBI
mouse Mus musculus High NCBI
rat Rattus norvegicus High NCBI

Life Stages


Life stage Evidence
Adult High

Sex Applicability


Term Evidence
Mixed High

Key Event Description


Goblet cells proliferate under normal conditions (Chopra et al., 1981) and in response to a variety of stimulants including EGF, viruses, bacteria and allergens (Ichinose et al., 2006; Camateros et al., 2007; Shatos et al., 2003; Duh et al., 2000; Tamaoki et al., 2004) in colon, eye, nose and lung. EGFR ligands EGF, HB-EGF and TGFA induce goblet cell proliferation through MAPK, p38 and JNK in cultured conjunctival and bronchial goblet cells (Booth et al., 2001; Booth et al., 2007; Gu et al., 2008; Shatos et al., 2003).

How It Is Measured or Detected


Various methods for measuring cell proliferation exist, and eventually, the test system and desired readout will determine which of these methods is selected. There are a number of recent reviews of available methods, their principle, advantages and drawbacks (Riss et al., 2013; Yadav et al., 2014; Adan et al., 2016; Romar et al., 2016).

Domain of Applicability


Proliferation of goblet cells was reported in human, mouse and rat (Tamaoki et al., 2004; Ichinose et al., 2006; Camateros et al., 2007; Shatos et al., 2003; Duh et al., 2000; Sydlik et al., 2006; Taniguchi et al., 2011).



Adan, A., Kiraz, Y., & Baran, Y. (2016). Cell proliferation and cytotoxicity assays. Curr Pharm Biotechnol 17, 1213-1221.

Booth, B.W., Adler, K.B., Bonner, J.C., Tournier, F., and Martin, L.D. (2001). Interleukin-13 induces proliferation of human airway epithelial cells in vitro via a mechanism mediated by transforming growth factor-alpha. Am J Respir Cell Mol Biol 25, 739–743.

Booth, B.W., Sandifer, T., Martin, E.L., and Martin, L.D. (2007). IL-13-induced proliferation of airway epithelial cells: mediation by intracellular growth factor mobilization and ADAM17. Respir Res 8, 51.

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.

Chopra, D.P., Yeh, K., and Brockman, R.W. (1981). Isolation and characterization of epithelial cell types from the normal rat colon. Cancer Res 41, 168–175.

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.

Gu, J., Chen, L., Shatos, M.A., Rios, J.D., Gulati, A., Hodges, R.R., and Dartt, D.A. (2008). Presence of EGF growth factor ligands and their effects on cultured rat conjunctival goblet cell proliferation. Exp Eye Res 86, 322–334.

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.

Riss TL, Moravec RA, Niles AL, et al. Cell Viability Assays. 2013 May 1 [Updated 2016 Jul 1]. In: Sittampalam GS, Coussens NP, Brimacombe K, et al., editors. Assay Guidance Manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2004-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK144065/
Romar, G. A., Kupper, T. S., & Divito, S. J. (2016). Research Techniques Made Simple: Techniques to Assess Cell Proliferation. J Invest Dermatol 136, e1-e7.

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.

Sydlik, U., Bierhals, K., Soufi, M., Abel, J., Schins, R.P.F., and Unfried, K. (2006). Ultrafine carbon particles induce apoptosis and proliferation in rat lung epithelial cells via specific signaling pathways both using EGF-R. Am J Physiol Lung Cell Mol Physiol 291, L725–L733.

Tamaoki, J., Isono, K., Takeyama, K., Tagaya, E., Nakata, J., and Nagai, A. (2004). Ultrafine carbon black particles stimulate proliferation of human airway epithelium via EGF receptor-mediated signaling pathway. Am J Physiol Lung Cell Mol Physiol 287, L1127–L1133.

Taniguchi, K., Yamamoto, S., Aoki, S., Toda, S., Izuhara, K., and Hamasaki, Y. (2011). Epigen is induced during the interleukin-13-stimulated cell proliferation in murine primary airway epithelial cells. Exp Lung Res 37, 461–470.

Yadav, K. , Singhal, N. , Rishi, V. and Yadav, H. (2014). Cell Proliferation Assays. In eLS, John Wiley & Sons, Ltd (Ed.). doi:10.1002/9780470015902.a0002566