The Unfolded Protein Response in Renal Transplantation pp. 163-177
Authors: (Nicolas Pallet, INSERM U775 and Paris Descartes University, Paris, France, and others)
Abstract: Endoplasmic reticulum (ER) stress is a consequence of the accumulation of misfolded proteins in the endoplasmic reticulum, triggering an evolutionarily conserved adaptive response termed the unfolded protein response. When the adaptive response fails, excessive ER stress triggers cell suicide. Important roles for ER-initiated cell death pathways have been recognized for several diseases, including diabetes, hypoxia, nutrient shortage, neurodegenerative and heart diseases. The implications of ER stress are not well recognized in solid organ transplantation, but increasing evidence suggests it has implications in mediating allograft injury. The purpose of this review is to summarize the mechanisms of ER stress and to discuss its implications during tissue injury in kidney transplantation. We will also discuss the possible implications of endoplasmic reticulum stress, beyond the scope of adaptation and cell death, in the modifications of cell functional properties and phenotypic changes. Increasing our understanding of the cellular and molecular mechanisms of acute and chronic allograft damages may lead to the development of new biomarkers and to the discovery of new therapeutic strategies to prevent the initiation of graft dysfunction or to promote tissue regeneration after injury.