Approximately 70% of kidney grafts are obtained from deceased donors, and these grafts must be preserved in hypothermic conditions to prolong their viability until transplantation. However, prolonged cold storage (CS) of kidneys results in poor long-term outcomes after transplantation. We reported previously that CS of rat kidneys for 18 h prior to transplant impaired proteasome function, disrupted protein homeostasis, and reduced graft function. The goal of the present study was to identify the renal proteins that are dysregulated by this CS-induced injury. Isolated donor Lewis rat kidneys were subject to 18-h CS and transplanted into recipient Lewis rats (CS+Tx). Autotransplantation (ATx: transplant with 0-h CS) or Sham (right nephrectomy) surgeries served as controls. The proteome of kidney homogenates was analyzed with tandem mass-tag mass spectrometry to identify CS-induced abnormalities in kidney grafts. CS injury disrupted the renal phosphoproteome in kidney grafts and dysregulated numerous signaling pathways. Integrated analysis of global proteomes and phosphoproteomes identified 15 proteins that were significantly regulated in a CS-specific manner. In particular, proteins and pathways such as complement and coagulation cascades were upregulated, while antioxidant pathways, such as glutathione, were suppressed in CS+Tx groups compared to ATx and Sham controls. This study, for the first time, provides deeper insight into the disruption of the renal graft proteome caused by CS injury and provides a novel set of pathways and molecules that can be investigated to delineate their specific role in renal transplant outcomes, ultimately improving outcomes for patients with end-stage kidney disease.
[doi:10.25345/C58K7574N]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Kidney transplant ; cold storage
Principal Investigators: (in alphabetical order) |
Nirmala Parajuli, University of Arkansas for Medical Sciences, United States |
Submitting User: | sbyrum |
Number of Files: | |
Total Size: | |
Spectra: | |
Subscribers: | |
Owner | Reanalyses | |
---|---|---|
Experimental Design | ||
Conditions:
|
||
Biological Replicates:
|
||
Technical Replicates:
|
||
Identification Results | ||
Proteins (Human, Remapped):
|
||
Proteins (Reported):
|
||
Peptides:
|
||
Variant Peptides:
|
||
PSMs:
|
||
Quantification Results | ||
Differential Proteins:
|
||
Quantified Proteins:
|
||
Browse Dataset Files | Browse Results |
FTP Download Link (click to copy):
|