title: Pathophysiological role of different tubular epithelial cell death modes in acute kidney injury.
abstract: The histological substrate of many forms of intrinsic acute kidney injury (AKI) has been classically attributed to tubular necrosis. However, more recent studies indicate that necrosis is not the main form of cell death in AKI and that other forms such as apoptosis, regulated necrosis (i.e. necroptosis and parthanatos), autophagic cell death and mitotic catastrophe, also participate in AKI and that their contribution depends on the cause and stage of AKI. Herein, we briefly summarize the main characteristics of the major types of cell death and we also critically review the existing evidence on the occurrence of different types of cell death reported in the most common experimental models of AKI and human specimens. We also discuss the pathophysiological mechanisms linking tubule epithelial cell death with reduced glomerular filtration, azotaemia and hydroelectrolytic imbalance. For instance, special relevance is given to the analysis of the inflammatory component of some forms of cell death over that of others, as an important and differential pathophysiological determinant. Finally, known molecular mechanisms and signalling pathways involved in each cell death type pose appropriate targets to specifically prevent or reverse AKI, provided that further knowledge of their participation and repercussion in each AKI syndrome is progressively increased in the near future.
authors.affiliation: Departamento de Fisiología y Farmacología , Universidad de Salamanca , Salamanca , Spain ; Instituto de Investigación Biomédica de Salamanca (IBSAL) , Salamanca , Spain ; Instituto Reina Sofía de Investigación Nefrológica, Fundación Iñigo Álvarez de Toledo , Madrid , Spain.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Sancho-Martínez
authors.affiliation: Departamento de Fisiología y Farmacología , Universidad de Salamanca , Salamanca , Spain ; Instituto de Investigación Biomédica de Salamanca (IBSAL) , Salamanca , Spain ; Instituto Reina Sofía de Investigación Nefrológica, Fundación Iñigo Álvarez de Toledo , Madrid , Spain ; Critical Care Biomedical Research Group (BioCritic) , Valladolid , Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: López-Novoa
authors.affiliation: Departamento de Fisiología y Farmacología , Universidad de Salamanca , Salamanca , Spain ; Instituto de Investigación Biomédica de Salamanca (IBSAL) , Salamanca , Spain ; Instituto Reina Sofía de Investigación Nefrológica, Fundación Iñigo Álvarez de Toledo , Madrid , Spain ; Critical Care Biomedical Research Group (BioCritic) , Valladolid , Spain ; Instituto de Estudios de Ciencias de la Salud de Castilla y León (IESCYL) , Salamanca , Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Hernández
keywords: apoptosis; autophagy; ferroptosis; necroptosis; pathophysiology