Mapping early serum proteome signatures of liver regeneration in living donor liver transplant cases

The liver is the only solid organ capable of regenerating itself to regain 100% of its mass and function after liver injury and/or partial hepatectomy (PH). This exceptional property represents a therapeutic opportunity for severe liver disease patients. However, liver regeneration (LR) might fail d...

Descripción completa

Detalles Bibliográficos
Autores: Carmona-Rodríguez, Lorena, Gajadhar, Aaron S., Blázquez-García, Irene, Guerrero, Laura, Fernández-Rojo, Manuel A., Uriarte, Iker, Mamani-Huanca, Maricruz, López-Gonzálvez, Ángeles, Ciordia, Sergio, Ramos, Antonio, Herrero, José Ignacio, Fernández-Barrena, Maite G., Arechederra, María, Berasain, Carmen, Quiroga, Jorge, Sangro, Bruno, Argemi, Josepmaría, Pardo, Fernando, Rotellar, Fernando, López-Serrano, Daniel, Barbas, Coral, Ávila, Matías A., Corrales, Fernando J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/363601
Acceso en línea:http://hdl.handle.net/10261/363601
https://api.elsevier.com/content/abstract/scopus_id/85159108099
Access Level:acceso abierto
Palabra clave:LDLT
SureQuant
differential proteomics
liver regeneration
phosphoproteomics
serum proteomics
Descripción
Sumario:The liver is the only solid organ capable of regenerating itself to regain 100% of its mass and function after liver injury and/or partial hepatectomy (PH). This exceptional property represents a therapeutic opportunity for severe liver disease patients. However, liver regeneration (LR) might fail due to poorly understood causes. Here, we have investigated the regulation of liver proteome and phosphoproteome at a short time after PH (9 h), to depict a detailed mechanistic background of the early LR phase. Furthermore, we analyzed the dynamic changes of the serum proteome and metabolome of healthy living donor liver transplant (LDLT) donors at different time points after surgery. The molecular profiles from both analyses were then correlated. Insulin and FXR-FGF15/19 signaling were stimulated in mouse liver after PH, leading to the activation of the main intermediary kinases (AKT and ERK). Besides, inhibition of the hippo pathway led to an increased expression of its target genes and of one of its intermediary proteins (14-3-3 protein), contributing to cell proliferation. In association with these processes, metabolic reprogramming coupled to enhanced mitochondrial activity cope for the energy and biosynthetic requirements of LR. In human serum of LDLT donors, we identified 56 proteins and 13 metabolites statistically differential which recapitulate some of the main cellular processes orchestrating LR in its early phase. These results provide mechanisms and protein mediators of LR that might prove useful for the follow-up of the regenerative process in the liver after PH as well as preventing the occurrence of complications associated with liver resection.

Similares en LA Referencia