Retinoid mediated protection against AKI during aging

Beth Israel Deaconess Medical Center, Boston MA

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Acute kidney injury (AKI) is a debilitating syndrome with a poor prognosis and increased mortality rate when it occurs in the setting of intensive hospital care. The increased frequency of occurrence of AKI in the older adults and the lasting impact that it makes in the quality of life and expectancy is a growing concern that needs to be addressed. There is immense interest in identifying molecular and cellular pathways that facilitate efficient renal repair in order to devise new therapeutic strategies against AKI in the elderly population. Several recent studies have demonstrated the activation of developmentally important signaling pathways during injury and regeneration in multiple adult tissue types. Retinoic acid (RA) signaling is one such pathway that is critically important for the proper development of many organs including the embryonic kidney. While there are studies including ours demonstrating the beneficial effects of exogenous administration of RA in multiple kidney injury models including AKI in the young kidneys, there is lack of evidence for a possible protective effect of exogenous RA administration against AKI in the aged kidneys following acute injury / repair. Also there is a lack of mechanistic insights of RA action and importantly, evidence towards the reactivation of endogenous RA signaling/pathway and the renal cell populations that are responsive to exogenous RA. Therefore, an investigation into the plausible reactivation or lack thereof of endogenous RA signaling pathway during kidney injury in the aged kidneys is highly imperative and will be key towards RA based pharmacological intervention in the future. Thus, in this research proposal we seek (i) to understand the protective effects of RA in the aged kidneys during acute injury and the effect of exogenous RA on the important players that determine the outcome of AKI, such as renal tubular epithelial cells and immune cells (ii) to study the exact functional role and status of endogenous RA signaling pathway in the aged kidneys during acute kidney injury / repair using mice models of AKI. A better understanding of the RA signaling pathway in the aged kidneys during AKI will help develop effective retinoid based therapeutic modalities for the prevention and / or treatment of AKI in the older adults.