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@ARTICLE{Muenchau:143645,
author = {S. Muenchau and R. Deutsch and I. J. de Castro and T.
Hielscher$^*$ and N. Heber and B. Niesler and M. Lusic and
M. L. Stanifer and S. Boulant$^*$},
title = {{H}ypoxic environment promotes barrier formation in human
intestinal epithelial cells through regulation of
mi{RNA}-320a expression.},
journal = {Molecular and cellular biology},
volume = {39},
number = {14},
issn = {1098-5549},
address = {Washington, DC},
publisher = {Soc.},
reportid = {DKFZ-2019-01219},
pages = {e00553-18},
year = {2019},
abstract = {Intestinal epithelial cells (IECs) are exposed to the
low-oxygen environment present in the lumen of the gut.
These hypoxic conditions are on one hand fundamental for the
survival of the commensal microbiota, and on the other hand,
favor the formation of a selective semipermeable barrier
allowing IECs to transport essential nutrients/water while
keeping the sterile internal compartments separated from the
lumen containing commensals. The hypoxia-inducible factor
(HIF) complex, which allows cells to respond and adapt to
fluctuations in oxygen levels, has been described as a key
regulator in maintaining IEC barrier function by regulating
their tight junction integrity. In this study, we sought to
better evaluate the mechanisms by which low oxygen
conditions impact the barrier function of human IECs. By
profiling miRNA expression in IECs under hypoxia, we
identified miRNA-320a as a novel barrier formation
regulator. Using pharmacological inhibitors and short
hairpin RNA-mediated silencing we could demonstrate that
expression of this miRNA was HIF-dependent. Importantly,
using over-expression and knock-down approaches of
miRNA-320a we could confirm its direct role in the
regulation of barrier functions in human IECs. These results
reveal an important link between miRNA expression and
barrier integrity, providing a novel insight into mechanisms
of hypoxia-driven epithelial homeostasis.},
cin = {C060 / F140},
ddc = {570},
cid = {I:(DE-He78)C060-20160331 / I:(DE-He78)F140-20160331},
pnm = {316 - Infections and cancer (POF3-316)},
pid = {G:(DE-HGF)POF3-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31061092},
doi = {10.1128/MCB.00553-18},
url = {https://inrepo02.dkfz.de/record/143645},
}