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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Mol+Cell+Proteomics
2014 ; 13
(12
): 3421-34
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Label-free quantitative urinary proteomics identifies the arginase pathway as a
new player in congenital obstructive nephropathy
#MMPMID25205225
Lacroix C
; Caubet C
; Gonzalez-de-Peredo A
; Breuil B
; Bouyssié D
; Stella A
; Garrigues L
; Le Gall C
; Raevel A
; Massoubre A
; Klein J
; Decramer S
; Sabourdy F
; Bandin F
; Burlet-Schiltz O
; Monsarrat B
; Schanstra JP
; Bascands JL
Mol Cell Proteomics
2014[Dec]; 13
(12
): 3421-34
PMID25205225
show ga
Obstructive nephropathy is a frequently encountered situation in newborns. In
previous studies, the urinary peptidome has been analyzed for the identification
of clinically useful biomarkers of obstructive nephropathy. However, the urinary
proteome has not been explored yet and should allow additional insight into the
pathophysiology of the disease. We have analyzed the urinary proteome of newborns
(n = 5/group) with obstructive nephropathy using label free quantitative
nanoLC-MS/MS allowing the identification and quantification of 970 urinary
proteins. We next focused on proteins exclusively regulated in severe obstructive
nephropathy and identified Arginase 1 as a potential candidate molecule involved
in the development of obstructive nephropathy, located at the crossroad of pro-
and antifibrotic pathways. The reduced urinary abundance of Arginase 1 in
obstructive nephropathy was verified in independent clinical samples using both
Western blot and MRM analysis. These data were confirmed in situ in kidneys
obtained from a mouse obstructive nephropathy model. In addition, we also
observed increased expression of Arginase 2 and increased total arginase activity
in obstructed mouse kidneys. mRNA expression analysis of the related arginase
pathways indicated that the pro-fibrotic arginase-related pathway is activated
during obstructive nephropathy. Taken together we have identified a new actor in
the development of obstructive nephropathy in newborns using quantitative urinary
proteomics and shown its involvement in an in vivo model of disease. The present
study demonstrates the relevance of such a quantitative urinary proteomics
approach with clinical samples for a better understanding of the pathophysiology
and for the discovery of potential therapeutic targets.