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Hypoxia Inducible Factor (HIF) Hydroxylases as Regulators of Intestinal
Epithelial Barrier Function
#MMPMID28462372
Manresa MC
; Taylor CT
Cell Mol Gastroenterol Hepatol
2017[May]; 3
(3
): 303-315
PMID28462372
show ga
Human health is dependent on the ability of the body to extract nutrients,
fluids, and oxygen from the external environment while at the same time
maintaining a state of internal sterility. Therefore, the cell layers that cover
the surface areas of the body such as the lung, skin, and gastrointestinal mucosa
provide vital semipermeable barriers that allow the transport of essential
nutrients, fluid, and waste products, while at the same time keeping the internal
compartments free of microbial organisms. These epithelial surfaces are highly
specialized and differ in their anatomic structure depending on their location to
provide appropriate and effective site-specific barrier function. Given this
important role, it is not surprising that significant disease often is associated
with alterations in epithelial barrier function. Examples of such diseases
include inflammatory bowel disease, chronic obstructive pulmonary disease, and
atopic dermatitis. These chronic inflammatory disorders often are characterized
by diminished tissue oxygen levels (hypoxia). Hypoxia triggers an adaptive
transcriptional response governed by hypoxia-inducible factors (HIFs), which are
repressed by a family of oxygen-sensing HIF hydroxylases. Here, we review recent
evidence suggesting that pharmacologic hydroxylase inhibition may be of
therapeutic benefit in inflammatory bowel disease through the promotion of
intestinal epithelial barrier function through both HIF-dependent and
HIF-independent mechanisms.
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