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@ARTICLE{Sharma:130550,
author = {K. R. Sharma and K. Heckler and S. J. Stoll$^*$ and J.-L.
Hillebrands and K. Kynast and E. Herpel and S. Porubsky and
M. Elger and B. Hadaschik and K. Bieback and H.-P. Hammes
and P. P. Nawroth and J. Kroll$^*$},
title = {{ELMO}1 protects renal structure and ultrafiltration in
kidney development and under diabetic conditions.},
journal = {Scientific reports},
volume = {6},
number = {1},
issn = {2045-2322},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2017-05629},
pages = {37172},
year = {2016},
abstract = {Engulfment and cell motility 1 (ELMO1) functions as a
guanine exchange factor for Rac1 and was recently found to
protect endothelial cells from apoptosis. Genome wide
association studies suggest that polymorphisms within human
elmo1 act as a potential contributing factor for the
development of diabetic nephropathy. Yet, the function of
ELMO1 with respect to the glomerulus and how this protein
contributes to renal pathology was unknown. Thus, this study
aimed to identify the role played by ELMO1 in renal
development in zebrafish, under hyperglycaemic conditions,
and in diabetic nephropathy patients. In zebrafish,
hyperglycaemia did not alter renal ELMO1 expression.
However, hyperglycaemia leads to pathophysiological and
functional alterations within the pronephros, which could be
rescued via ELMO1 overexpression. Zebrafish ELMO1 crispants
exhibited a renal pathophysiology due to increased apoptosis
which could be rescued by the inhibition of apoptosis. In
human samples, immunohistochemical staining of ELMO1 in
nondiabetic, diabetic and polycystic kidneys localized ELMO1
in glomerular podocytes and in the tubules. However, ELMO1
was not specifically or distinctly regulated under either
one of the disease conditions. Collectively, these results
highlight ELMO1 as an important factor for glomerular
protection and renal cell survival via decreasing apoptosis,
especially under diabetic conditions.},
cin = {A190},
ddc = {000},
cid = {I:(DE-He78)A190-20160331},
pnm = {321 - Basic Concepts (POF3-321)},
pid = {G:(DE-HGF)POF3-321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27849017},
pmc = {pmc:PMC5111104},
doi = {10.1038/srep37172},
url = {https://inrepo02.dkfz.de/record/130550},
}