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Key Event Title
Increase, Proliferation of goblet cells
Key Event Components
|cell proliferation||goblet cell||increased|
Key Event Overview
AOPs Including This Key Event
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).
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.
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