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000130550 0247_ $$2doi$$a10.1038/srep37172
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000130550 037__ $$aDKFZ-2017-05629
000130550 041__ $$aeng
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000130550 1001_ $$aSharma, Krishna Rakesh$$b0
000130550 245__ $$aELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions.
000130550 260__ $$aLondon$$bNature Publishing Group$$c2016
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000130550 520__ $$aEngulfment and cell motility 1 (ELMO1) functions as a guanine exchange factor for Rac1 and was recently found to protect endothelial cells from apoptosis. Genome wide association studies suggest that polymorphisms within human elmo1 act as a potential contributing factor for the development of diabetic nephropathy. Yet, the function of ELMO1 with respect to the glomerulus and how this protein contributes to renal pathology was unknown. Thus, this study aimed to identify the role played by ELMO1 in renal development in zebrafish, under hyperglycaemic conditions, and in diabetic nephropathy patients. In zebrafish, hyperglycaemia did not alter renal ELMO1 expression. However, hyperglycaemia leads to pathophysiological and functional alterations within the pronephros, which could be rescued via ELMO1 overexpression. Zebrafish ELMO1 crispants exhibited a renal pathophysiology due to increased apoptosis which could be rescued by the inhibition of apoptosis. In human samples, immunohistochemical staining of ELMO1 in nondiabetic, diabetic and polycystic kidneys localized ELMO1 in glomerular podocytes and in the tubules. However, ELMO1 was not specifically or distinctly regulated under either one of the disease conditions. Collectively, these results highlight ELMO1 as an important factor for glomerular protection and renal cell survival via decreasing apoptosis, especially under diabetic conditions.
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000130550 7001_ $$aHeckler, Karl$$b1
000130550 7001_ $$0P:(DE-HGF)0$$aStoll, Sandra J$$b2
000130550 7001_ $$0P:(DE-HGF)0$$aHillebrands, Jan-Luuk$$b3
000130550 7001_ $$aKynast, Katharina$$b4
000130550 7001_ $$aHerpel, Esther$$b5
000130550 7001_ $$0P:(DE-HGF)0$$aPorubsky, Stefan$$b6
000130550 7001_ $$aElger, Marlies$$b7
000130550 7001_ $$aHadaschik, Boris$$b8
000130550 7001_ $$aBieback, Karen$$b9
000130550 7001_ $$aHammes, Hans-Peter$$b10
000130550 7001_ $$aNawroth, Peter P$$b11
000130550 7001_ $$0P:(DE-HGF)0$$aKroll, Jens$$b12$$eLast author
000130550 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/srep37172$$gVol. 6, no. 1, p. 37172$$n1$$p37172$$tScientific reports$$v6$$x2045-2322$$y2016
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