Difference between revisions of "Event:920"

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== Evidence Supporting Taxonomic Applicability ==
 
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Goblet cell metaplasia has been observed extensively in human (Gomperts et al. 2007), (Laoukili et al., 2001), (Yoshisue and Hasegawa, 2004), (Turner et al., 2011), (Casalino-Matsuda et al., 2006) and moderately in mouse (Fujisawa et al., 2008), (Tyner et al., 2006). Studies in rat have documented goblet cell increase but did not directly measure transdifferentiation of ciliated to goblet cells.
  
 
== References ==
 
== References ==
  
 
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Revision as of 00:53, 22 April 2016


Event Title

Metaplasia of goblet cells, Increase

Key Event Overview

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AOPs Including This Key Event

AOP Name Event Type Essentiality
EGFR Activation Leading to Mucus Hypersecretion KE Moderate

Taxonomic Applicability

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

Level of Biological Organization

Biological Organization
Tissue

How this Key Event works

Metaplasia is the replacement of a differentiated cell type with another differentiated cell type. In the case of goblet cell metaplasia, ciliated or Clara cells transdifferentiate into goblet cells (Tyner et al., 2006), (Evans et al., 2004), leading to an increased number of mucus-producing cells and eventually mucus hypersecretion. There is an inverse relationship between goblet cell metaplasia and FEV1, a measure of lung function (Shao et al., 2004).

Ozone and endotoxin induce mucus cell metaplasia in rat airway epithelium (Harkema and Hotchkiss, 1993)


Increased EGFR expression is associated with bronchial metaplasia (Kurie et al., 1996).

How it is Measured or Detected

Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible?

In vitro/in vivo experiments

Studies measure metaplasia by looking for co-expression of cell markers or characteristics from two different cell types: the originating cell that is differentiating into the goblet cell. Both Clara and ciliated cells have been studied as goblet cell progenitors: CSSP is used as a Clara cell marker (Reader et al., 2003), (Hayashi et al., 2004), (Evans et al., 2004), while FOXJ1, beta-tubulin, tektin and DNAH9 are used as ciliated markers (Yoshisue and Hasegawa, 2004), (Gomperts et al. 2007), (Turner et al., 2011), (Fujisawa et al., 2008). Apical localization of ezrin, ciliary beat frequency and glutamuylated tubulins are other characteristics of ciliated cells (Laoukili et al., 2001). Transdifferentiation and metaplasia are said to occur when these Clara cell and ciliated cell characteristics and markers decrease while goblet cell markers increase, MUC5AC and other mucin proteins. Electron or fluorescence microscopy is used to show co-expression of markers and a transitory cell type (observation of goblet and cilia cell features within the same cell) (Tyner et al., 2006), (Laoukili et al., 2001), (Gomperts et al., 2007).

Another definition of metaplasia that is used in the literature is detection of increased mucus. Increased mucus is detected using Alcian blue/periodic acid-Schiff (AB/PAS) for detection of mucin glycoproteins. In cell and animal experiments, literature often equates an increase in mucus production with "mucus metaplasia" even though the study did not look at the origin of cells to see if they were differentiated from non-goblet cells. This definition is often used for hyperplasia as well.

Clinical

Metaplasia is assessed by a pathologist by the replacement of cells that are not normally at that location.

Evidence Supporting Taxonomic Applicability

Goblet cell metaplasia has been observed extensively in human (Gomperts et al. 2007), (Laoukili et al., 2001), (Yoshisue and Hasegawa, 2004), (Turner et al., 2011), (Casalino-Matsuda et al., 2006) and moderately in mouse (Fujisawa et al., 2008), (Tyner et al., 2006). Studies in rat have documented goblet cell increase but did not directly measure transdifferentiation of ciliated to goblet cells.

References