Transplantation · 2025
Cold Storage Disrupts the Proteome and Phosphoproteome Landscape in Rat Kidney Transplants.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sharma Amod, Jun Se-Ran, Bhattarai Dinesh, Panday Sudip, Venugopal Gopinath, Panawan Orasa, Washam Charity, Mackintosh Samuel, Byrum Stephanie, Udaondo Zulema, Arthur John M, MacMillan-Crow Lee Ann, Parajuli Nirmala
Аннотация
BACKGROUND: Prolonged cold storage (CS) of kidneys results in poor long-term outcomes after transplantation (Tx). We reported previously that CS of rat kidneys for 18 h before transplant impaired proteasome function, disrupted protein homeostasis, and reduced graft function. The goal of the present study was to identify the renal proteins, including phosphoproteins, that are dysregulated by this CS injury.
METHODS: Isolated donor Lewis rat kidneys were subject to 18 h CS and transplanted into recipient Lewis rats (CS + Tx). Autotransplantation (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.
RESULTS: CS injury disrupted the renal proteome/phosphoproteome landscape in kidney grafts and dysregulated numerous signaling pathways. We identified 3217 phosphopeptides (with 1398 novel phosphosites) that were significantly dysregulated in a CS-specific manner. In particular, proteins and pathways such as complement system and mitogen-activated protein kinases, including p38MAPK, were upregulated, whereas antioxidant/metabolic pathways, such as glutathione, were suppressed in CS + Tx groups compared with autotransplantation and sham controls.
CONCLUSIONS: This study provides deeper insight into the disruption of the renal proteome/phosphoproteome caused by CS injury and provides a novel set of pathways and molecules, including p38MAPK, that can be investigated to delineate their specific role in renal transplant outcomes, ultimately improving outcomes for patients with end-stage kidney disease.
METHODS: Isolated donor Lewis rat kidneys were subject to 18 h CS and transplanted into recipient Lewis rats (CS + Tx). Autotransplantation (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.
RESULTS: CS injury disrupted the renal proteome/phosphoproteome landscape in kidney grafts and dysregulated numerous signaling pathways. We identified 3217 phosphopeptides (with 1398 novel phosphosites) that were significantly dysregulated in a CS-specific manner. In particular, proteins and pathways such as complement system and mitogen-activated protein kinases, including p38MAPK, were upregulated, whereas antioxidant/metabolic pathways, such as glutathione, were suppressed in CS + Tx groups compared with autotransplantation and sham controls.
CONCLUSIONS: This study provides deeper insight into the disruption of the renal proteome/phosphoproteome caused by CS injury and provides a novel set of pathways and molecules, including p38MAPK, that can be investigated to delineate their specific role in renal transplant outcomes, ultimately improving outcomes for patients with end-stage kidney disease.