Mechanisms of regulation of normal and metaplastic intestinal differentiation
2018
The gastrointestinal tract is an organized
structure originating from the three embryonic germ
layers: endoderm, mesoderm and ectoderm.
Morphological changes that accompany its formation are
relatively well known, although the underlying
molecular mechanisms are still poorly defined. Intestinal
metaplasia, resulting from an epithelial transdifferentiation
process, is considered a precursor lesion
of gastric adenocarcinoma, a malignancy with serious
consequences in terms of morbidity and mortality
worldwide. Similarly to gastrointestinal embryonic
development, molecular changes involved in the
development of this lesion that recapitulate the intestinal
development, out of time and space, are also widely
unknown.
In this review we present, briefly, the process of
formation of the digestive tract, from its embryonic age
to adulthood, with emphasis on anterior-posterior
patterning and on molecular mechanisms that may play
an important role. In addition, we try to establish a
parallel and understand what mechanisms can, through
their deregulation, originate the metaplastic lesion.
Cdx genes appear to be the main regulators of
normal intestinal differentiation and also to be largely
involved in the metaplastic epithelial transdifferentiation
process. However, control of gene expression both
during intestinal development and in intestinal metaplasia is complex and seems to depend on several
transcription factors. More extensive studies about the
mechanisms underlying intestinal metaplasia are needed
if we aim to prevent neoplasia development and all its
negative consequences in persons at risk.
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